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Xu Z, Mousavi T, Ainslie M. Numerical simulation of magnetic drug targeting for lung cancer therapy using a bulk superconducting magnet. Drug Deliv 2025; 32:2490836. [PMID: 40299317 PMCID: PMC12042242 DOI: 10.1080/10717544.2025.2490836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 02/28/2025] [Accepted: 04/03/2025] [Indexed: 04/30/2025] Open
Abstract
Primary bronchus cancer is one kind of lung cancer with a very high mortality rate. Magnetic drug targeting (MDT) technology could concentrate drugs in a specific area, which could have useful application in lung cancer therapy. Due to a bulk superconducting magnet's ability to generate a superior magnetic field strength and gradient in comparison to conventional permanent magnets, there is great potential for achieving MDT external to the body. However, current research in this area is still in its infancy, and numerical simulations exploring the guidance ability of this technology have been limited to only two-dimensional geometries, which limits further exploration toward clinical transformation. In this work, a three-dimensional lung and bulk superconducting magnet model have been built in the finite-element software package COMSOL Multiphysics. The model is used to simulate the drug delivery process in the lung via the superconducting magnet. The influence of various parameters on the capture efficiency is investigated, including lung-magnet distance, bulk superconductor properties, particle properties, and physiological or tumor structural parameters. The results demonstrate that the bulk superconducting magnet can effectively improve the capture efficiency of magnetic drugs or drug carriers within a suitable distance outside of the body, which could potentially guide the design of a practical, external superconducting MDT system in the near future.
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Affiliation(s)
- Zhenyang Xu
- Department of Engineering, King’s College London, London, UK
| | - Tayebeh Mousavi
- Department of Engineering, King’s College London, London, UK
| | - Mark Ainslie
- Department of Engineering, King’s College London, London, UK
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2
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Lozano-García M, Dikici E, Bilbao D, Mohan P, Deo S, Daunert S. Multifunctional delivery strategies and nanoplatforms of SN-38 in cancer therapeutics. J Control Release 2025; 384:113937. [PMID: 40490199 DOI: 10.1016/j.jconrel.2025.113937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 06/03/2025] [Accepted: 06/05/2025] [Indexed: 06/11/2025]
Abstract
SN-38 or 7-ethyl-10-hydroxycamptothecin is the active metabolite of irinotecan, a widely used chemotherapeutic agent for the treatment of colorectal, pancreatic, lung, breast, gastric, esophageal, hepatocellular, ovarian, brain, leukemia, and lymphoma malignancies. SN-38's antitumoral effect is 100 to 1000 times more potent than that of irinotecan. However, its clinical application is hindered by its poor solubility and chemical instability. To circumvent these challenges and avoid systemic toxicities, such as myelosuppression and diarrhea, several SN-38 delivery systems have been explored. In that regard, formulations based on targeted, controlled and tumor-responsive release of SN-38 have demonstrated to enhance its antitumoral effects and reduce the associated systemic toxicities by limiting the pharmacological activity to the desired tumor location. To this end, prodrugs, conjugates, nanoparticles, dendrimers, or lipid-based strategies for SN-38 delivery have been used. Most recently, multifunctional approaches have emerged as an attractive alternative to develop SN-38 delivery systems, combining several strategies in a single formulation, i.e., encapsulating nanocarriers, tumor-targeting ligands, stimuli-responsive elements, optimal linkers, drug combinations or bioimaging agents. Despite their therapeutic advantages, multifunctional delivery systems often face challenges concerning their clinical translation compared to conventional therapies, such as biocompatibility, scalability and cost-effectiveness issues. The aim of this work is to review the most recent progress that has been made in the development and assessment of multifunctional delivery systems for cancer treatment.
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Affiliation(s)
- Mercedes Lozano-García
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute (BioNIUM), University of Miami, Miami, FL 33136, USA
| | - Emre Dikici
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute (BioNIUM), University of Miami, Miami, FL 33136, USA
| | - Daniel Bilbao
- Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute (BioNIUM), University of Miami, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA; Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Prasoon Mohan
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute (BioNIUM), University of Miami, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA; Vascular and Interventional Radiology, University of Miami Health System, Miami, FL 33136, USA
| | - Sapna Deo
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute (BioNIUM), University of Miami, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA
| | - Sylvia Daunert
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute (BioNIUM), University of Miami, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA; Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
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3
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Kalındemirtaş FD, Cilasun GE, Kariper A. Enhanced therapeutic efficacy of platinum-doxorubicin nanoparticles on colon and breast cancer cell lines. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04080-4. [PMID: 40299021 DOI: 10.1007/s00210-025-04080-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Accepted: 03/19/2025] [Indexed: 04/30/2025]
Abstract
In this study, platinum nanoparticles (PtNPs) were synthesized and their potential to improve the efficacy of doxorubicin (DOX) in cancer treatment was investigated. H2PtCl6, LiAlH4, and trisodium citrate were used during the synthesis of PtNPs. They were characterized using dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), and scanning transmission electron microscopy (STEM). The diameter of the PtNPs was measured to be 21.72 nm without DOX loading and approximately 212 nm after DOX loading (DOX-PtNPs). FTIR confirmed the binding of DOX to PtNPs. In addition, MTT assays showed that DOX-PtNPs have a stronger effect on MCF-7 and HCT116 cancer cells than free DOX, even at low doses. The IC50 value for MCF-7 cells treated with DOX was determined to be 4.81 µg/ml, while it was significantly lower for the DOX-PtNP group at 0.64 µg/ml. A similar trend was observed in HCT116 cells, where the IC50 value for DOX was 5.03 µg/ml, while for DOX-PtNPs it was 0.62 µg/ml. In summary, the activity of DOX in these cells was increased approximately eightfold by PtNPs. Moreover, DOX-PtNPs showed no significant cytotoxic effects on normal HUVEC cells at low doses. Moreover, DOX-PtNPs enhanced apoptotic activity in HCT116 cells without inducing drug resistance as demonstrated by Rho123 staining and annexin/PI analyses. The significance of this study lies in the pioneering use of DOX-PtNPs in colon cancer, the synthesis of smaller PtNPs, the eightfold increase in the efficacy of DOX, and the demonstration that DOX-PtNPs do not significantly increase drug resistance.
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Affiliation(s)
| | - Gökçe Erdemir Cilasun
- Department of Medical Biology, Faculty of Medicine, Biruni University, Istanbul, Turkey
| | - Afşin Kariper
- Department of Science Education, Education Faculty, Erciyes University, Kayseri, Turkey
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Huang L, Ni W, Jia Y, Zhu M, Yang T, Yu M, Zhang J. Process Development for the Continuous Manufacturing of Carbamazepine-Nicotinamide Co-Crystals Utilizing Hot-Melt Extrusion Technology. Pharmaceutics 2025; 17:568. [PMID: 40430860 PMCID: PMC12115052 DOI: 10.3390/pharmaceutics17050568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2025] [Revised: 04/18/2025] [Accepted: 04/21/2025] [Indexed: 05/29/2025] Open
Abstract
Objectives: Hot-melt extrusion (HME) offers a solvent-free, scalable approach for manufacturing pharmaceutical co-crystals (CCs), aligning with the industry's shift to continuous manufacturing (CM). However, challenges like undefined yield optimization, insufficient risk management, and limited process analytical technology (PAT) integration hinder its industrial application. This study aimed to develop a proof-of-concept HME platform for CCs, assess process risks, and evaluate PAT-enabled monitoring to facilitate robust production. Methods: Using carbamazepine (CBZ) and nicotinamide (NIC) as model compounds, an HME platform compatible with PAT tools was established. A systematic risk assessment identified five key risk domains: materials, machinery, measurement, methods, and other factors. A Box-Behnken design of experiments (DoE) evaluated the impact of screw speed, temperature, and mixing sections on CC quality. Near-infrared (NIR) spectroscopy monitored CBZ-NIC co-crystal formation in real time during HME process. Results: DoE revealed temperature and number of mixing sections significantly influenced particle size (D50: 2.0-4.0 μm), while screw speed affected efficiency. NIR spectroscopy detected a unique CC absorption peak at 5008.3 cm⁻¹, enabling real-time structural monitoring with high accuracy (R² = 0.9999). Risk assessment highlighted material attributes, process parameters, and equipment design as critical factors affecting CC formation. All experimental batches yielded ≥ 94% pure CCs with no residual starting materials, demonstrating process reproducibility and robustness. Conclusions: Overall, this work successfully established a continuous hot-melt extrusion (HME) process for manufacturing CBZ-NIC co-crystals, offering critical insights into material, equipment, and process parameters while implementing robust in-line NIR monitoring for real-time quality control. Additionally, this work provides interpretable insights and serves as a basis for future machine learning (ML)-driven studies.
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Affiliation(s)
- Lianghao Huang
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Pharmaceutical Products Research and Development Center, Marine Biomedical Research Institute of Qingdao, Qingdao 266137, China
| | - Wen Ni
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Pharmaceutical Products Research and Development Center, Marine Biomedical Research Institute of Qingdao, Qingdao 266137, China
| | - Yaru Jia
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Pharmaceutical Products Research and Development Center, Marine Biomedical Research Institute of Qingdao, Qingdao 266137, China
| | - Minqing Zhu
- Material Characterization, Thermo Fisher Scientific, Shanghai 201203, China;
| | - Tiantian Yang
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Pharmaceutical Products Research and Development Center, Marine Biomedical Research Institute of Qingdao, Qingdao 266137, China
| | - Mingchao Yu
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Pharmaceutical Products Research and Development Center, Marine Biomedical Research Institute of Qingdao, Qingdao 266137, China
| | - Jiaxiang Zhang
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
- Pharmaceutical Products Research and Development Center, Marine Biomedical Research Institute of Qingdao, Qingdao 266137, China
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Mandal M, Banerjee I, Mandal M. Effective approaches in conquering chemoresistance of glioblastoma: potential for nanoformulations. Drug Deliv Transl Res 2025:10.1007/s13346-025-01859-z. [PMID: 40259195 DOI: 10.1007/s13346-025-01859-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/10/2025] [Indexed: 04/23/2025]
Abstract
Glioblastoma Multiforme is an aggressive and complex cancer affecting mostly elderly patients above the age of 60 years. Originally classified as the fourth stage of glioma, it has an abysmal prognosis along with limited therapeutic options. Surgical removal of tumors, radiotherapy, and chemotherapy are prevalent treatment strategies with numerous therapeutic obstacles, including undefined boundary of tumor mass leaving traces even after excision, chances of secondary cancer formation, and presence of blood-brain barrier. These blood-brain and blood-brain tumor barriers actively restrict the permeability of many molecules from blood circulation to enter the central nervous system. Therefore, many conventional antineoplastic drugs fail to reach the tumor periphery except temozolomide. Meanwhile, active stem cells in the tumor microenvironment, genetic mutation inducing tumor growth, and epigenetic pattern alteration make this cancer chemoresistant. Our review delineates the recent approaches to resensitize the existing clinical drugs through specifically designed nanoformulations. Nanoparticles with modified physiological characteristics and modified through technological parameters can reduce the tumor's stemness, which increases tumor cells' apoptosis rate. Moreover, these nanoparticles can efficiently traverse the blood-brain barrier and escape from endosomal degradation with minimum toxicological impact. Overall, this review discusses the cancer chemoresistance phenomena and related pathways and highlights the potential of nanoformulation in reversing chemoresistance. Also, the existing limitations of this unique approach and suggestions are discussed at the end of the article, which may facilitate the identification of new directions for advancement of the nanoparticle-mediated reversal of chemoresistance.
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Affiliation(s)
- Madhurima Mandal
- School of Medical Science & Technology, Indian Institute of Technology, Kharagpur, West Bengal, 721302, India
| | - Indranil Banerjee
- Department of Pharmaceutical Technology, JIS University, 81, Nilgunj Road, Agarpara, Kolkata, West Bengal, 700109, India.
| | - Mahitosh Mandal
- School of Medical Science & Technology, Indian Institute of Technology, Kharagpur, West Bengal, 721302, India.
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Sharma R, Kumar S, Komal K, Ghosh R, Thakur S, Pal RR, Kumar M. Comprehensive insights into pancreatic cancer treatment approaches and cutting-edge nanocarrier solutions: from pathology to nanomedicine. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04094-y. [PMID: 40202672 DOI: 10.1007/s00210-025-04094-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Accepted: 03/21/2025] [Indexed: 04/10/2025]
Abstract
Pancreatic cancer is one of the most lethal malignancies worldwide. It is characterized by poor prognosis, high mortality, and recurrence rates. Various modifiable and non-modifiable risk factors are associated with pancreatic cancer incidence. Available treatments for pancreatic cancer include surgery, chemotherapy, radiotherapy, photodynamic therapy, supportive care, targeted therapy, and immunotherapy. However, the survival rates for PC are very low. Regrettably, despite efforts to enhance prognosis, the survival rate of pancreatic cancer remains relatively low. Therefore, it is essential to investigate new approaches to improve pancreatic cancer treatment. By synthesizing current knowledge and identifying existing gaps, this article provides a comprehensive overview of risk factors, pathology, conventional treatments, targeted therapies, and recent advancements in nanocarriers for its treatment, along with various clinical trials and patents that justify the safety and efficacy of innovative carriers for drug delivery systems. Ultimately, this review underscores the potential of these innovative formulations to improve outcomes and contribute significantly to the advancement of Pancreatic Cancer treatment. Together, these insights highlight nano-formulations as a promising frontier for effectively treating Pancreatic Cancer.
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Affiliation(s)
- Rohit Sharma
- Department of Pharmaceutics, ISF College Pharmacy, GT Road, Moga, 142001, Punjab, India
| | - Sourabh Kumar
- Department of Pharmaceutics, ISF College Pharmacy, GT Road, Moga, 142001, Punjab, India
| | - Kumari Komal
- Department of Pharmaceutics, ISF College Pharmacy, GT Road, Moga, 142001, Punjab, India
| | - Rashmi Ghosh
- Department of Pharmaceutics, ISF College Pharmacy, GT Road, Moga, 142001, Punjab, India
| | - Shubham Thakur
- Department of Pharmaceutics, ISF College Pharmacy, GT Road, Moga, 142001, Punjab, India
| | - Ravi Raj Pal
- Department of Pharmaceutics, ISF College Pharmacy, GT Road, Moga, 142001, Punjab, India
| | - Manish Kumar
- Department of Pharmaceutics, ISF College Pharmacy, GT Road, Moga, 142001, Punjab, India.
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Madineh H, Mansourinia F, Zarrintaj P, Poostchi M, Gnatowski P, Kucinska-Lipka J, Ghaffari M, Hasanin MS, Chapi S, Yazdi MK, Ashrafizadeh M, Bączek T, Saeb MR, Wang G. Stimuli-responsive delivery systems using carbohydrate polymers: A review. Int J Biol Macromol 2025; 310:142648. [PMID: 40174846 DOI: 10.1016/j.ijbiomac.2025.142648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Revised: 03/08/2025] [Accepted: 03/27/2025] [Indexed: 04/04/2025]
Abstract
Carbohydrate polymers, including Chitosan, Cellulose, Starch, Dextran, Pectin, Alginate, and Hyaluronic Acid, have been considered as stimuli-responsive biopolymers demonstrating significant potential for drug delivery approaches. Relying on the specific design and fabrication, such biopolymers are able to respond to fluctuations in pH, temperature, or enzymatic activity. This review investigates stimuli-responsive biopolymers, known as carbohydrate polymers, mainly chitosan, cellulose, and alginate, utilized as drug delivery approaches, emphasizing that these stimuli-responsive biopolymers accelerate controlled drug release. The pH-responsive delivery systems selectively target acidic tumor microenvironments, while temperature-responsive materials provide precise control for drug release produced by hyperthermia. Light-responsive biopolymers provide spatial and temporal control, providing appropriate for targeted therapy. Redox-responsive structures are especially efficient in responding to elevated glutathione (GSH) in tumor microenvironment, facilitating targeted drug release. Electro- and magnetic-responsive systems provide remote control functionalities, improving the accuracy of drug administration. The incorporation of multi-stimuli-responsive mechanisms implies a remarkable progression in drug delivery, providing a more versatile and adaptable framework for therapeutic applications. Accordingly, the future research on carbohydrate polymer-based stimuli-responsive delivery systems should focus on improving the responsiveness and targeting efficacy through complicated optimization of features and performance of carbohydrate polymers, where the integration of multifunctional moieties facilitates transformation of targeted drugs for broader biological functions.
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Affiliation(s)
- Hossein Madineh
- Polymer Engineering Department, Chemical Engineering Faculty, Tarbiat Modares University, Tehran, Iran
| | - Fatemeh Mansourinia
- Polymer Engineering Department, Chemical Engineering Faculty, Tarbiat Modares University, Tehran, Iran
| | | | - Maryam Poostchi
- Department of Polymer Technology, Faculty of Chemistry, Gdańsk University of Technology, Gabriela Narutowicza 11/12, 80-233 Gdańsk, Poland
| | - Przemysław Gnatowski
- Department of Polymer Technology, Faculty of Chemistry, Gdańsk University of Technology, Gabriela Narutowicza 11/12, 80-233 Gdańsk, Poland; Department of Environmental Toxicology, Faculty of Health Sciences with the Institute of Maritime and Tropical Medicine, Medical University of Gdańsk, Dębowa 23A, Gdańsk 80-204, Poland.
| | - Justyna Kucinska-Lipka
- Department of Polymer Technology, Faculty of Chemistry, Gdańsk University of Technology, Gabriela Narutowicza 11/12, 80-233 Gdańsk, Poland
| | - Mehdi Ghaffari
- Polymer Group, Faculty of Technical and Engineering, Golestan University, P. O. Box 155, Gorgan, Golestan, Iran
| | - Mohamed S Hasanin
- Cellulose and Paper Department, National Research Centre, 33 El Bohouth St., Cairo 12622, Egypt; Department of Polymer and Biomaterials Science, West Pomeranian University of Technology in Szczecin, Al. Piastow 45, 70-311 Szczecin, Poland
| | - Sharanappa Chapi
- Department of Physics, B.M.S. College of Engineering, Basavanagudi - 560019, Bengaluru, Karnataka, India
| | - Mohsen Khodadadi Yazdi
- Division of Electrochemistry and Surface Physical Chemistry, Faculty of Applied Physics and Mathematics, Gdańsk University of Technology, Narutowicza 11/12, 80-233 Gdańsk, Poland; Advanced Materials Center, Gdańsk University of Technology, Narutowicza 11/12, 80-233 Gdańsk, Poland
| | - Milad Ashrafizadeh
- Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China
| | - Tomasz Bączek
- Department of Pharmaceutical Chemistry, Medical University of Gdańsk, J. Hallera 107, 80-416 Gdańsk, Poland
| | - Mohammad Reza Saeb
- Department of Pharmaceutical Chemistry, Medical University of Gdańsk, J. Hallera 107, 80-416 Gdańsk, Poland.
| | - Guizhen Wang
- Department of Emergency, Shanghai Tenth People's Hospital, School of Medicine Tongji University, Shanghai 200072, China.
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Chattopadhyay S, Goswami A, Sil M. Nanobiotechnology: traditional re-interpreting personalized medicine through targeted therapies and regenerative solutions. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04038-6. [PMID: 40100374 DOI: 10.1007/s00210-025-04038-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Accepted: 03/07/2025] [Indexed: 03/20/2025]
Abstract
Nanobiotechnology is transforming personalized medicine by leveraging the unique properties of nanomaterials to address key challenges in targeted drug delivery, regenerative medicine, and diagnostics. The development of nanocarriers, such as liposomes, polymeric nanoparticles, dendrimers, and metallic nanoparticles, has enabled precise drug delivery with enhanced bioavailability and reduced systemic toxicity. Concurrently, nanostructured scaffolds have advanced regenerative medicine by supporting stem cell differentiation, modulating cellular microenvironments, and enhancing tissue repair. These nanoscale innovations have also led to highly sensitive biosensors and imaging agents, significantly improving early disease detection and biomarker monitoring. Despite these advancements, challenges persist, including nanoparticle-induced cytotoxicity, immunogenicity, scalability issues, and regulatory hurdles requiring extensive evaluation of long-term biocompatibility and pharmacokinetics. Addressing these limitations, recent breakthroughs in AI-assisted nanotechnology and CRISPR-Cas9-mediated gene editing are driving next-generation precision medicine, integrating nanoscale therapeutics with computational approaches to enhance efficacy. Future directions focus on nanorobotics, bioengineered nanovaccines, and theranostic platforms capable of simultaneous diagnosis and treatment, paving the way for real-time, patient-specific interventions. The successful translation of nanomedicine into clinical practice will require interdisciplinary collaboration across nanoscience, bioengineering, and translational medicine to refine nanoparticle functionalization, optimize safety profiles, and ensure equitable access to nanotherapeutics. This review provides a comprehensive overview of these advancements, challenges, and emerging opportunities in nanobiotechnology-driven precision medicine.
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Affiliation(s)
- Sayantani Chattopadhyay
- Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Chennai, 603203, Tamil Nadu, India
| | - Arunava Goswami
- Biological Sciences Division, Indian Statistical Institute, 203 B. T. Road, Kolkata, 700108, West Bengal, India.
| | - Moumita Sil
- Biological Sciences Division, Indian Statistical Institute, 203 B. T. Road, Kolkata, 700108, West Bengal, India.
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Pouyan A, Ghorbanlo M, Eslami M, Jahanshahi M, Ziaei E, Salami A, Mokhtari K, Shahpasand K, Farahani N, Meybodi TE, Entezari M, Taheriazam A, Hushmandi K, Hashemi M. Glioblastoma multiforme: insights into pathogenesis, key signaling pathways, and therapeutic strategies. Mol Cancer 2025; 24:58. [PMID: 40011944 PMCID: PMC11863469 DOI: 10.1186/s12943-025-02267-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 02/07/2025] [Indexed: 02/28/2025] Open
Abstract
Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary brain tumor in adults, characterized by a poor prognosis and significant resistance to existing treatments. Despite progress in therapeutic strategies, the median overall survival remains approximately 15 months. A hallmark of GBM is its intricate molecular profile, driven by disruptions in multiple signaling pathways, including PI3K/AKT/mTOR, Wnt, NF-κB, and TGF-β, critical to tumor growth, invasion, and treatment resistance. This review examines the epidemiology, molecular mechanisms, and therapeutic prospects of targeting these pathways in GBM, highlighting recent insights into pathway interactions and discovering new therapeutic targets to improve patient outcomes.
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Affiliation(s)
- Ashkan Pouyan
- Department of Neurosurgery, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Masoud Ghorbanlo
- Department of Anesthesiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Masoud Eslami
- Department of Neurosurgery, Kerman University of Medical Sciences, Kerman, Iran
| | - Majid Jahanshahi
- Department of Neurosurgery, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ehsan Ziaei
- Department of Neurosurgery, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ali Salami
- Department of Neurosurgery, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Khatere Mokhtari
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Koorosh Shahpasand
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- Department of Laboratory Medicine and Pathology, Institute for Translational Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Najma Farahani
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Tohid Emami Meybodi
- Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran.
- Functional Neurosurgery Research Center, Shohada Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Maliheh Entezari
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Afshin Taheriazam
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
- Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Kiavash Hushmandi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
- Department of Epidemiology, University of Tehran, Tehran, Iran.
| | - Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
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Zhang N, Zhang T, Feng J, Shang J, Zhang B, Dong Q, Zhang Z, Sun C. Application of therapeutical nanoparticles with neutrophil membrane camouflaging for inflammatory plaques targeting against atherosclerosis. Mater Today Bio 2025; 30:101397. [PMID: 39802828 PMCID: PMC11722182 DOI: 10.1016/j.mtbio.2024.101397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 11/30/2024] [Accepted: 12/09/2024] [Indexed: 01/16/2025] Open
Abstract
Atherosclerosis is the leading cause of cardiovascular disease and myocardial infarction. Precise and effective plaque targeting is a major objective for therapeutic outcomes throughout various stages of atherosclerosis. Inspired by the natural recruitment of neutrophils in atherosclerotic plaques, we fabricated a simvastatin (ST)-loaded and neutrophil membrane-cloaked nanoplatform (NNPST) for enhancing localized payload delivery and atherosclerosis management. The resulting NNPST mimicked neutrophil function and significantly decreased macrophage-mediated phagocytosis to prolong its own circulation time in the blood. Compared to pristine nanoparticles (NPST) without a membrane coating, NNPST achieved better plaque targeting in ApoE-/- mice, as indicated by neutrophils actively recruited in atherosclerotic lesions. The higher plaque homing with NNPST was monitored by dynamic fluorescence/magnetic resonance (MR) dual-modality imaging. The results further showed that NNPST efficiently prevented atherosclerosis development mainly by suppressing local inflammatory macrophages, and the percentage of plaques in the entire aortic area was reduced to 4.75 ± 1.48 % following NNPST treatment. A biosafety assessment indicated that the biomimetic NNPST induced no noticeable toxicity in the body. This approach of neutrophil membrane-camouflaged nanoparticles offers new opportunities to various therapeutic agents for on-demand delivery in neutrophil-involved inflammatory diseases.
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Affiliation(s)
- Ningnannan Zhang
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, 300052, PR China
| | - Tianzhu Zhang
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, 300052, PR China
| | - Jintang Feng
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, 300052, PR China
| | - Jian Shang
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, 300052, PR China
| | - Beibei Zhang
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450002, PR China
| | - Qingyang Dong
- Department of Environmental Medicine, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, PR China
| | - Zhang Zhang
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, 300052, PR China
| | - Chunyang Sun
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, 300052, PR China
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11
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Bełdzińska P, Galikowska-Bogut B, Zakrzewski M, Bury K, Jamrógiewicz M, Wyrzykowski D, Gołuński G, Sądej R, Piosik J. Platinum as both a drug and its modulator - Do platinum nanoparticles influence cisplatin activity? Chem Biol Interact 2025; 407:111365. [PMID: 39743036 DOI: 10.1016/j.cbi.2024.111365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 12/19/2024] [Accepted: 12/29/2024] [Indexed: 01/04/2025]
Abstract
Breast cancer was the most frequent cause of cancer death in females in 2022. Despite the development of personalized therapies, chemotherapy frequently remains the only available treatment method. However, the administration of classic antineoplastic drugs, like cisplatin (CDDP), often causes severe side effects and may lead to drug resistance making the therapy inefficient. Therefore, there is a great need for new, effective treatment regimens development. For this reason, we applied platinum nanoparticles (PtNPs) to verify if they can influence the CDDP activity with particular emphasis on the differences due to nanoparticles' sizes. We employed a broad spectrum of physicochemical methods, including Dynamic Light Scattering, Atomic Force Microscopy, Isothermal Titration Calorimetry, Fourier Transform Infrared Spectroscopy, and Near Infrared Spectroscopy and also Differential Scanning Calorimetry, to characterize the possible interactions between nanoparticles and CDDP. Moreover, the impact of PtNPs on CDDP biological activity was investigated using the Ames mutagenicity test on Salmonella enterica serovar Typhimurium TA102 and MTT assay on two breast cancer cell lines MDA-MB-231 and SKBR3. The obtained results revealed PtNPs direct interactions with CDDP dependent on the nanoparticles' size. Despite the lack of explicit confirmation of PtNPs aggregation by AFM imaging and DLS, further physicochemical methods indicated structural changes between nanoparticles alone and PtNPs-CDDP mixtures. Moreover, the biological assays confirmed that PtNPs decrease CDDP mutagenicity and also slightly increase its cytotoxicity on the chosen cell lines. The latter effects are ambiguous, nevertheless, provide a valuable basis for further research.
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Affiliation(s)
| | | | | | - Katarzyna Bury
- Laboratory of Molecular Biology, University of Gdańsk, Gdańsk, Poland
| | | | - Dariusz Wyrzykowski
- Department of General and Inorganic Chemistry, University of Gdansk, Gdansk, Poland
| | | | - Rafał Sądej
- Laboratory of Molecular Enzymology and Oncology, Medical University of Gdańsk, Gdańsk, Poland
| | - Jacek Piosik
- Laboratory of Biophysics, University of Gdańsk, Gdańsk, Poland.
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12
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Sriram A, Ithape H, Singh PK. Deep-insights: Nanoengineered gel-based localized drug delivery for arthritis management. Asian J Pharm Sci 2025; 20:101012. [PMID: 39995751 PMCID: PMC11848107 DOI: 10.1016/j.ajps.2024.101012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 05/15/2024] [Accepted: 07/03/2024] [Indexed: 02/26/2025] Open
Abstract
Arthritis is an inflammatory joint disorder that progressively impairs function and diminishes quality of life. Conventional therapies often prove ineffective, as oral administration lacks specificity, resulting in off-target side effects like hepatotoxicity and GIT-related issues. Intravenous administration causes systemic side effects. The characteristic joint-localized symptoms such as pain, stiffness, and inflammation make the localized drug delivery suitable for managing arthritis. Topical/transdermal/intra-articular routes have become viable options for drug delivery in treating arthritis. However, challenges with those localized drug delivery routes include skin barrier and cartilage impermeability. Additionally, conventional intra-articular drug delivery also leads to rapid clearance of drugs from the synovial joint tissue. To circumvent these limitations, researchers have developed nanocarriers that enhance drug permeability through skin and cartilage, influencing localized action. Gel-based nanoengineered therapy employs a gel matrix to incorporate the drug-encapsulated nanocarriers. This approach combines the benefits of gels and nanocarriers to enhance therapeutic effects and improve patient compliance. This review emphasizes deep insights into drug delivery using diverse gel-based novel nanocarriers, exploring their various applications embedded in hyaluronic acid (biopolymer)-based gels, carbopol-based gels, and others. Furthermore, this review discusses the influence of nanocarrier pharmacokinetics on the localization and therapeutic manipulation of macrophages mediated by nanocarriers. The ELVIS (extravasation through leaky vasculature and inflammatory cell-mediated sequestration) effect associated with arthritis is advantageous in drug delivery. Simply put, the ELVIS effect refers to the extravasation of nanocarriers through leaky vasculatures, which finally results in the accumulation of nanocarriers in the joint cavity.
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Affiliation(s)
| | | | - Pankaj Kumar Singh
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Telangana 500037, India
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13
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Miranda-Vera C, Hernández ÁP, García-García P, Díez D, García PA, Castro MÁ. Bioconjugation of Podophyllotoxin and Nanosystems: Approaches for Boosting Its Biopharmaceutical and Antitumoral Profile. Pharmaceuticals (Basel) 2025; 18:169. [PMID: 40005983 PMCID: PMC11859694 DOI: 10.3390/ph18020169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/19/2025] [Accepted: 01/22/2025] [Indexed: 02/27/2025] Open
Abstract
Podophyllotoxin is a natural compound belonging to the lignan family and is well-known for its great antitumor activity. However, it shows several limitations, such as severe side effects and some pharmacokinetics problems, including low water solubility, which hinders its application as an anticancer agent. Over the past few years, antitumor research has been focused on developing nanotechnology-based medicines or nanomedicines which allow researchers to improve the pharmacokinetic properties of anticancer compounds. Following this trend, podophyllotoxin nanoconjugates have been obtained to overcome its biopharmaceutical drawbacks and to enhance its antitumor properties. The objective of this review is to highlight the advances made over the past few years (2017-2023) regarding the inclusion of podophyllotoxin in different nanosystems. Among the huge variety of nanoconjugates of diverse nature, drug delivery systems bearing podophyllotoxin as cytotoxic payload are organic nanoparticles mainly based on polymer carriers, micelles, and liposomes. Along with the description of their pharmacological properties as antitumorals and the advantages compared to the free drug in terms of biocompatibility, solubility, and selectivity, we also provide insight into the synthetic procedures developed to obtain those podophyllotoxin-nanocarriers. Typical procedures in this regard are self-assembly techniques, nanoprecipitations, or ionic gelation methods among others. This comprehensive perspective aims to enlighten the medicinal chemistry community about the tendencies followed in the design of new podophyllotoxin-based drug delivery systems, their features and applications.
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Affiliation(s)
- Carolina Miranda-Vera
- Laboratorio de Química Farmacéutica, Departamento de Ciencias Farmacéuticas, CIETUS, IBSAL, Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37007 Salamanca, Spain; (C.M.-V.); (Á.-P.H.); (P.G.-G.); (P.A.G.)
| | - Ángela-Patricia Hernández
- Laboratorio de Química Farmacéutica, Departamento de Ciencias Farmacéuticas, CIETUS, IBSAL, Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37007 Salamanca, Spain; (C.M.-V.); (Á.-P.H.); (P.G.-G.); (P.A.G.)
| | - Pilar García-García
- Laboratorio de Química Farmacéutica, Departamento de Ciencias Farmacéuticas, CIETUS, IBSAL, Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37007 Salamanca, Spain; (C.M.-V.); (Á.-P.H.); (P.G.-G.); (P.A.G.)
| | - David Díez
- Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad de Salamanca, 37008 Salamanca, Spain;
| | - Pablo A. García
- Laboratorio de Química Farmacéutica, Departamento de Ciencias Farmacéuticas, CIETUS, IBSAL, Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37007 Salamanca, Spain; (C.M.-V.); (Á.-P.H.); (P.G.-G.); (P.A.G.)
| | - María Ángeles Castro
- Laboratorio de Química Farmacéutica, Departamento de Ciencias Farmacéuticas, CIETUS, IBSAL, Facultad de Farmacia, Campus Miguel de Unamuno, Universidad de Salamanca, 37007 Salamanca, Spain; (C.M.-V.); (Á.-P.H.); (P.G.-G.); (P.A.G.)
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14
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Kim C, Nan J, Nguyen KT, Park JO, Choi E, Kim J. Non-FFP-Based Magnetic Particle Imaging (NFMPI) with an Open-Type RF Coil System: A Feasibility Study. SENSORS (BASEL, SWITZERLAND) 2025; 25:665. [PMID: 39943301 PMCID: PMC11821019 DOI: 10.3390/s25030665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 01/16/2025] [Accepted: 01/21/2025] [Indexed: 02/16/2025]
Abstract
Active drug delivery systems for cancer therapy are gaining attention for their biocompatibility and enhanced efficacy compared to conventional chemotherapy and surgery. To improve precision in targeted drug delivery (TDD), actuating devices using external magnetic fields are employed. However, a key challenge is the inability to visually track magnetic drug carriers in blood vessels, complicating navigation to the target. Magnetic particle imaging (MPI) systems can localize magnetic carriers (MCs) but rely on bulky electromagnetic coils to generate a static magnetic field gradient, creating a field-free point (FFP) within the field of view (FOV). Also, additional coils are required to move the FFP across the FOV, limiting flexibility and increasing the system size. To address these issues, we propose a non-FFP-based, open-type RF coil system with a simplified structure composed of a Tx/Rx coil and a permanent magnet at the coil center, eliminating the need for an FFP. Furthermore, integrating a robotic arm for coil assembly enables easy adjustment of the FOV size and location. Finally, imaging tests with magnetic nanoparticles (MNPs) confirmed the system's ability to detect and localize a minimum mass of 0.3 mg (Fe) in 80 × 80 mm2.
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Affiliation(s)
- Chan Kim
- Korea Institute of Medical Microrobotics, Gwangju 61186, Republic of Korea; (C.K.); (K.T.N.); (J.-O.P.)
| | - Jiyun Nan
- School of Mechanical Engineering, Chonnam National University, Gwangju 61186, Republic of Korea;
| | - Kim Tien Nguyen
- Korea Institute of Medical Microrobotics, Gwangju 61186, Republic of Korea; (C.K.); (K.T.N.); (J.-O.P.)
| | - Jong-Oh Park
- Korea Institute of Medical Microrobotics, Gwangju 61186, Republic of Korea; (C.K.); (K.T.N.); (J.-O.P.)
| | - Eunpyo Choi
- School of Mechanical Engineering, Chonnam National University, Gwangju 61186, Republic of Korea;
| | - Jayoung Kim
- Department of Biosystems Engineering, Chungbuk National University, Cheongju 28644, Republic of Korea
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15
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Kedar P, Saraf A, Maheshwari R, Sharma M. Advances in Dendritic Systems and Dendronized Nanoparticles: Paradigm Shifts in Cancer Targeted Therapy and Diagnostics. Mol Pharm 2025; 22:28-57. [PMID: 39707984 DOI: 10.1021/acs.molpharmaceut.4c00856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2024]
Abstract
Cancer has emerged as a global health crisis, claiming millions of lives annually. Dendrimers and dendronized nanoparticles, a novel class of nanoscale molecules with highly branched three-dimensional macromolecular structures, have gained significant attention in cancer treatment and diagnosis due to their unique properties. These dendritic macromolecules offer a precisely controlled branching architecture, enabling functionalization with specific targeting molecules to enhance the selective delivery of therapeutic agents to tumor cells while minimizing systemic toxicity. Through surface modifications and the incorporation of various components, dendrimers demonstrate remarkable adaptability as nanocarriers for biomedical imaging and theranostic applications. Surface functionalization strategies, including PEGylation and ligand attachment (e.g., folic acid, RGD peptide, lactobionic acid), further enhance biocompatibility and facilitate targeted tumor cell imaging. Leveraging their improved biocompatibility and target specificity, dendritic nanosystems offer heightened sensitivity and precision in cancer diagnostics. Notably, the encapsulation of metal nanoparticles within dendrimers, such as gold nanoparticles, has shown promise in enhancing tumor imaging capabilities. Ongoing advancements in nanotechnology are poised to increase the sophistication and complexity of dendrimer-based systems, highlighting their potential as nanocarriers in drug delivery platforms, with a growing number of clinical trials on the horizon. This review provides a comprehensive overview of the potential and future prospects of dendrimers and dendrimer-based nanocarriers in targeted cancer therapy and diagnosis, exploring their ability to enhance biocompatibility, reduce toxicity, and improve therapeutic outcomes across various malignancies.
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Affiliation(s)
- Pawan Kedar
- School of Pharmacy and Technology Management, SVKM's Narsee Monjee Institute of Management Studies (NMIMS), Deemed to be University, Shirpur, Dhule, Maharashtra 425405, India
| | - Apeksha Saraf
- School of Pharmacy, Devi Ahilya Vishwavidyalaya, Takshashila Campus, Khandwa Road, Indore, Madhya Pradesh 452001, India
| | - Rahul Maheshwari
- School of Pharmacy and Technology Management, SVKM's Narsee Monjee Institute of Management Studies (NMIMS), Deemed to be University, Hyderabad 509301, India
| | - Mayank Sharma
- School of Pharmacy and Technology Management, SVKM's Narsee Monjee Institute of Management Studies (NMIMS), Deemed to be University, Shirpur, Dhule, Maharashtra 425405, India
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16
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Mohammed PN, Hussen NH, Hasan AH, Salh HJH, Jamalis J, Ahmed S, Bhat AR, Kamal MA. A review on the role of nanoparticles for targeted brain drug delivery: synthesis, characterization, and applications. EXCLI JOURNAL 2025; 24:34-59. [PMID: 39967907 PMCID: PMC11830919 DOI: 10.17179/excli2024-7163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 12/09/2024] [Indexed: 02/20/2025]
Abstract
Unfortunately, nowadays, brain disorders, which include both neurological and mental disorders, are the main cause of years spent living with a disability worldwide. There are serious diseases with a high prevalence and a high mortality rate. However, the outmoded technical infrastructure makes their treatment difficult. The blood-brain barrier (BBB) serves as a protective mechanism for the central nervous system (CNS) and regulates its homeostatic processes. The brain is protected against injury and illness by an extremely complex system that precisely regulates the flow of ions, very few tiny molecules, and an even smaller number of macromolecules from the blood to the brain. Nevertheless, the BBB also considerably inhibits the delivery of medications to the brain, making it impossible to treat a variety of neurological diseases. Several strategies are now being studied to enhance the transport of drugs over the BBB. According to this research, nanoparticles are one of the most promising agents for brain disease treatment while many conventional drugs are also capable of crossing this barrier but there are amazing facts about nanoparticles in brain drug delivery. For example, 1. Precision Targeting: Through mechanisms such as receptor-mediated transport, ligand attachment, or the use of external stimuli (e.g., magnetic or thermal guidance), nanoparticles can deliver drugs specifically to diseased areas of the brain while minimizing exposure to healthy tissues. This targeted approach reduces side effects and enhances therapeutic outcomes. 2. Improved Drug Stability: Drugs can be encapsulated by nanoparticles, which keeps them stable and shields them from deterioration while being transported to the brain. 3. Therapeutic Payload: Nanoparticles possess a high surface-area-to-volume ratio, enabling them to encapsulate a substantial quantity of therapeutic agents relative to their size. This allows for enhanced drug delivery efficiency, maximizing therapeutic outcomes while potentially reducing the required dosage to achieve the desired effect. 4. Imaging Properties: Certain nanoparticles can also act as contrast agents for magnetic resonance imaging (MRI), allowing for the real-time visualization of drug distribution and administration in the brain. 5. Combination Therapy Possibility: Nanoparticles can be designed to co-deliver multiple medications or therapeutic agents, which could enhance synergistic effects. There have been in vivo studies where nanoparticles were successfully used for combination therapies, demonstrating potential for personalized treatments. One notable example is in cancer treatment, where nanoparticles have been designed to co-deliver multiple chemotherapeutic agents. In general, brain medication delivery by nanoparticles is a novel strategy that has the potential to revolutionize neurological disease therapy and enhance patient outcomes. The study furthermore includes a concise depiction of the structural and physiological characteristics of the BBB, and it also provides an overview of the nanoparticles that are most often used in medicine. A brief overview of the structural and physiochemical characteristics of the NPs, as well as the most popular nanoparticles used in medicine, is also included in the review.
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Affiliation(s)
- Payam Nawzad Mohammed
- Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, University of Sulaimani, Sulaimani 46001, Kurdistan Region-Iraq, Iraq
| | - Narmin Hamaamin Hussen
- Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, University of Sulaimani, Sulaimani 46001, Kurdistan Region-Iraq, Iraq
| | - Aso Hameed Hasan
- Department of Chemistry, College of Science, University of Garmian, Kalar 46021, Kurdistan Region-Iraq, Iraq
- Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia- 81310 Johor Bahru, Johor, Malaysia
| | - Hozan Jaza Hama Salh
- Department of Clinical Pharmacy, College of Pharmacy, University of Sulaimani, Sulaimani 46001, Kurdistan Region, Iraq
| | - Joazaizulfazli Jamalis
- Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia- 81310 Johor Bahru, Johor, Malaysia
| | - Sumeer Ahmed
- Post-Graduate and Research Department of Chemistry, The New College (Autonomous), University of Madras, Chennai - 600014, India
| | - Ajmal R. Bhat
- Department of Chemistry, RTM Nagpur University, Nagpur- 440033, India
| | - Mohammad Amjad Kamal
- Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
- Department of Pharmacy, Faculty of Health and Life Sciences, Daffodil International University, Birulia, Savar, Dhaka -1216, Bangladesh
- Centre for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
- Novel Global Community Educational Foundation, Australia
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17
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Deshmukh V, Pathan NS, Haldar N, Nalawade S, Narwade M, Gajbhiye KR, Gajbhiye V. Exploring intranasal drug delivery via nanocarriers: A promising glioblastoma therapy. Colloids Surf B Biointerfaces 2025; 245:114285. [PMID: 39366109 DOI: 10.1016/j.colsurfb.2024.114285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 09/23/2024] [Accepted: 09/29/2024] [Indexed: 10/06/2024]
Abstract
Glioblastoma is one of the most recurring types of glioma, having the highest mortality rate among all other gliomas. Traditionally, the standard course of treatment for glioblastoma involved maximum surgical resection, followed by chemotherapy and radiation therapy. Nanocarriers have recently focused on enhancing the chemotherapeutic administration to the brain to satisfy unmet therapeutic requirements for treating brain-related disorders. Due to the significant drawbacks and high recurrence rates of gliomas, intranasal administration of nanocarrier systems presents several advantages. These include low toxicity, non-invasiveness, and the ability to cross the blood-brain barrier. By customizing their size, encasing them with mucoadhesive agents, or undergoing surface modification that encourages movement over the nose's mucosa, we can exceptionally engineer nanocarriers for intranasal administration. Olfactory and trigeminal nerves absorb drugs administered nasally and transport them to the brain, serving as the primary delivery mechanism for nose-to-brain administration. This review sums up the latest developments in chemotherapeutic nanocarriers, such as metallic nanoparticles, polymeric nanoparticles, nanogels, nano vesicular carriers, genetic material-based nanocarriers, and polymeric micelles. These nanocarriers have demonstrated efficient drug delivery from the nose to the brain, effectively overcoming mucociliary clearance. However, challenges persist, such as limitations in targeted chemotherapy and restricted drug loading capacity for intranasal administration. Additionally, the review addresses regulatory considerations and prospects for these innovative drug delivery systems.
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Affiliation(s)
- Vishawambhar Deshmukh
- Poona College of Pharmacy, Bharati Vidyapeeth Deemed to be University, Erandwane, Pune 411038, India
| | - Nida Sayed Pathan
- Nanobioscience Group, Agharkar Research Institute, Pune 411004, India
| | - Niladri Haldar
- Nanobioscience Group, Agharkar Research Institute, Pune 411004, India
| | - Shubhangi Nalawade
- Poona College of Pharmacy, Bharati Vidyapeeth Deemed to be University, Erandwane, Pune 411038, India
| | - Mahavir Narwade
- Poona College of Pharmacy, Bharati Vidyapeeth Deemed to be University, Erandwane, Pune 411038, India
| | - Kavita R Gajbhiye
- Poona College of Pharmacy, Bharati Vidyapeeth Deemed to be University, Erandwane, Pune 411038, India.
| | - Virendra Gajbhiye
- Nanobioscience Group, Agharkar Research Institute, Pune 411004, India.
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18
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Abawi A, Trunfio-Sfarghiu AM, Thomann C, Petiot E, Lollo G, Granjon T, Girard-Egrot A, Maniti O. Tailor-made vincristine-liposomes for tumor targeting. Biochimie 2024; 227:35-46. [PMID: 39094823 DOI: 10.1016/j.biochi.2024.07.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 07/22/2024] [Accepted: 07/30/2024] [Indexed: 08/04/2024]
Abstract
To ensure selective targeting based on membrane fluidity and physico-chemical compatibility between the biological membrane of the target cell and the lipid membrane of the liposomes carriers. Lipid-based carriers as liposomes with varying membrane fluidities were designed for delivering vincristine, an anti-tumor compound derived from Madagascar's periwinkle. Liposomes, loaded with vincristine, were tested on prostate, colon, and breast cancer cell lines alongside non-tumor controls. Results showed that vincristine-loaded liposomes with fluid membranes significantly decreased the viability of cancer cell lines compared to controls. Confocal microscopy revealed the intracellular release of vincristine, evidenced by disrupted mitosis-specific labeling of actin filaments in metastatic prostate cell lines. This highlights the crucial role of membrane fluidity in the development of lipid-based drug carriers, offering a promising and cost-effective option for targeting cancer cells as an alternative to conventional strategies.
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Affiliation(s)
- Ariana Abawi
- Institute of Molecular and Supramolecular Chemistry and Biochemistry, ICBMS UMR 5246, Univ. Lyon, University Lyon 1, CNRS, 69622, Lyon, France.
| | | | - Céline Thomann
- Institute of Molecular and Supramolecular Chemistry and Biochemistry, ICBMS UMR 5246, Univ. Lyon, University Lyon 1, CNRS, 69622, Lyon, France.
| | - Emma Petiot
- Institute of Molecular and Supramolecular Chemistry and Biochemistry, ICBMS UMR 5246, Univ. Lyon, University Lyon 1, CNRS, 69622, Lyon, France.
| | - Giovanna Lollo
- Laboratoire D'Automatique, de Génie des Procédés et de Génie Pharmaceutique, LAGEPP UMR 5007, University Lyon 1, CNRS, 69622, Lyon, France.
| | - Thierry Granjon
- Institute of Molecular and Supramolecular Chemistry and Biochemistry, ICBMS UMR 5246, Univ. Lyon, University Lyon 1, CNRS, 69622, Lyon, France.
| | - Agnès Girard-Egrot
- Institute of Molecular and Supramolecular Chemistry and Biochemistry, ICBMS UMR 5246, Univ. Lyon, University Lyon 1, CNRS, 69622, Lyon, France.
| | - Ofelia Maniti
- Institute of Molecular and Supramolecular Chemistry and Biochemistry, ICBMS UMR 5246, Univ. Lyon, University Lyon 1, CNRS, 69622, Lyon, France.
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19
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Cui X, He Z, Liang J, Wei M, Guo Z, Zhou Y, Qin Y, Deng Z. Dehydrocurvularin-loaded mPEG-PLGA nanoparticles for targeted breast cancer drug delivery: preparation, characterization, in vitro, and in vivo evaluation. J Drug Target 2024; 32:325-333. [PMID: 38269592 DOI: 10.1080/1061186x.2024.2309566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 11/09/2023] [Indexed: 01/26/2024]
Abstract
Dehydrocurvularin (DCV) is a promising lead compound for anti-cancer therapy. Unfortunately, the development of DCV-based drugs has been hampered by its poor solubility and bioavailability. Herein, we prepared a DCV-loaded mPEG-PLGA nanoparticles (DCV-NPs) with improved drug properties and therapeutic efficacy. The spherical and discrete particles of DCV-NPs had a uniform diameter of 101.8 ± 0.45 nm and negative zeta potential of -22.5 ± 1.12 mV (pH = 7.4), and its entrapment efficiency (EE) and drug loading (DL) were ∼53.28 ± 1.12 and 10.23 ± 0.30%, respectively. In vitro the release of DCV-NPs lasted for more than 120 h in a sustained-release pattern, its antiproliferation efficacy towards breast cancer cell lines (MCF-7, MDA-MB-231, and 4T1) was better than that of starting drug DCV, and it could be efficiently and rapidly internalised by breast cancer cells. In vivo DCV-NPs were gradually accumulated in tumour areas of mice and significantly suppressed tumour growth. In summary, loading water-insoluble DCV onto nanoparticles has the potential to be an effective agent for breast cancer therapy with injectable property and tumour targeting capacity.
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Affiliation(s)
- Xuewei Cui
- Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang, China
| | - Zhong He
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang, China
| | - Jianjia Liang
- Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang, China
| | - Mulan Wei
- Department of Pathology, Yiling Hospital Yichang, Yichang, China
| | - Zhiyong Guo
- Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang, China
| | - Yiqing Zhou
- School of Biotechnology and Food Engineering, Changshu Institute of Technology, Changshu, China
| | - Ye Qin
- State Key Laboratory of Drug Research, Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Zhangshuang Deng
- Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang, China
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20
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Surya C, Lakshminarayana ABV, Ramesh SH, Kunjiappan S, Theivendren P, Santhana Krishna Kumar A, Ammunje DN, Pavadai P. Advancements in breast cancer therapy: The promise of copper nanoparticles. J Trace Elem Med Biol 2024; 86:127526. [PMID: 39298835 DOI: 10.1016/j.jtemb.2024.127526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 08/12/2024] [Accepted: 09/05/2024] [Indexed: 09/22/2024]
Abstract
BACKGROUND Breast cancer (BC) is the most prevalent cancer among women worldwide and poses significant treatment challenges. Traditional therapies often lead to adverse side effects and resistance, necessitating innovative approaches for effective management. OBJECTIVE This review aims to explore the potential of copper nanoparticles (CuNPs) in enhancing breast cancer therapy through targeted drug delivery, improved imaging, and their antiangiogenic properties. METHODS The review synthesizes existing literature on the efficacy of CuNPs in breast cancer treatment, addressing common challenges in nanotechnology, such as nanoparticle toxicity, scalability, and regulatory hurdles. It proposes a novel hybrid method that combines CuNPs with existing therapeutic modalities to optimize treatment outcomes. RESULTS CuNPs demonstrate the ability to selectively target cancer cells while sparing healthy tissues, leading to improved therapeutic efficacy. Their unique physicochemical properties facilitate efficient biodistribution and enhanced imaging capabilities. Additionally, CuNPs exhibit antiangiogenic activity, which can inhibit tumor growth by preventing the formation of new blood vessels. CONCLUSION The findings suggest that CuNPs represent a promising avenue for advancing breast cancer treatment. By addressing the limitations of current therapies and proposing innovative solutions, this review contributes valuable insights into the future of nanotechnology in oncology.
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Affiliation(s)
- Chandana Surya
- Department of Pharmacognosy, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bangalore, Karnataka 560054, India
| | | | - Sameera Hammigi Ramesh
- Department of Pharmacology, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bangalore, Karnataka 560054, India
| | - Selvaraj Kunjiappan
- Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil, Tamilnadu 626126, India
| | - Panneerselvam Theivendren
- Department of Pharmaceutical Chemistry, Swamy Vivekananda College of Pharmacy, Elayampalayam, Namakkal, Tamilnadu 637205, India
| | - A Santhana Krishna Kumar
- Department of Chemistry, National Sun Yat-sen University, No. 70, Lien-hai Road, Gushan District, Kaohsiung City 80424, Taiwan; Department of Chemistry, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, Tamil Nadu 602105, India.
| | - Damodar Nayak Ammunje
- Department of Pharmacology, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bangalore, Karnataka 560054, India.
| | - Parasuraman Pavadai
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bangalore, Karnataka 560054, India.
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21
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Xu J, Xu X, Zhang H, Wu J, Pan R, Zhang B. Tumor-associated inflammation: The role and research progress in tumor therapy. J Drug Deliv Sci Technol 2024; 102:106376. [DOI: 10.1016/j.jddst.2024.106376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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22
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Basu S, Biswas P, Anto M, Singh N, Mukherjee K. Nanomaterial-enabled drug transport systems: a comprehensive exploration of current developments and future avenues in therapeutic delivery. 3 Biotech 2024; 14:289. [PMID: 39507057 PMCID: PMC11534931 DOI: 10.1007/s13205-024-04135-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 10/16/2024] [Indexed: 11/08/2024] Open
Abstract
Over the years, nanotechnology has gained popularity as a viable solution to address gene and drug delivery challenges over conventional methods. Extensive research has been conducted on nanosystems that consist of organic/inorganic materials, drugs, and its biocompatibility become the primary goal of improving drug delivery. Various surface modification methods help focus targeted and controlled drug release, further enabling multidrug delivery also. This newer technology ensures the stability of drugs that can unravel the mechanisms involved in cellular processes of disease development and its management. Tailored medication delivery provides benefits such as therapy, controlled release, and reduced adverse effects, which are especially important for controlling illnesses like cancer. However, multifunctional nanocarriers that possess high viscoelasticity, extended circulation half-life, biocompatibility, and biodegradability face some challenges and limitations too in human bodies. To produce a consistent therapeutic platform based on complex three-dimensional nanoparticles, careful design and engineering, thorough orthogonal analysis methods, and reproducible scale-up and manufacturing processes will be required in the future. Safety and effectiveness of nano-based drug delivery should be thoroughly investigated in preclinical and clinical trials, especially when considering biodistribution, targeting specific areas, and potential immunological toxicities. Overall, the current review article explores the advancements in nanotechnology, specific to nanomaterial-enabled drug delivery systems, carrier fabrication techniques and modifications, disease management, clinical research, applications, limitations, and future challenges. The work portrays how nanomedicine distribution affects healthcare with an emphasis on the developments in drug delivery techniques.
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Affiliation(s)
- Shatabdi Basu
- Amity Institute of Biotechnology, Amity University, Kolkata, West Bengal 700135 India
| | - Pragnya Biswas
- Department of Bioengineering and Biotechnology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835215 India
| | - Mariya Anto
- Department of Bioengineering and Biotechnology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835215 India
| | - Nandini Singh
- Department of Bioengineering and Biotechnology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835215 India
| | - Koel Mukherjee
- Department of Bioengineering and Biotechnology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835215 India
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23
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Massarotti M, Corna P, Mallik A, Milanesi G, Casali C, Magrassi L, Comincini S. Development and Biological Characterization of Cancer Biomimetic Membrane Nanovesicles for Enhancing Therapy Efficacy in Human Glioblastoma Cells. NANOMATERIALS (BASEL, SWITZERLAND) 2024; 14:1779. [PMID: 39591021 PMCID: PMC11597144 DOI: 10.3390/nano14221779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 10/31/2024] [Accepted: 11/04/2024] [Indexed: 11/28/2024]
Abstract
As nanocarriers of a new generation, biomimetic nanovesicles are an emerging class of therapeutic tools whose surface is integrated or fabricated with biomaterials capable of mimicking the biological features and functions of native cells. Thanks to this, biomimetic nanovesicles, in particular, those made by plasma membrane moieties, possess greatly improved biocompatibility, high target specificity, a long retention time, and minimal undesired immune responses. For these reasons, a multitude of progenitor cells including cancer ones were employed as templates to generate biomimetic or membrane-camouflaged nanovesicles hosting different therapeutic compounds. In this contribution, different membrane-derived biomimetic vesicles (M-NVs) were generated by osmotic lysis or plasma membrane isolation approaches from normal and cancer cell lines and assayed against in vitro models of human glioblastoma. M-NVs were compared in their cellular internalization degrees of DNA and proteins, morphologically and molecularly characterized, expressing an extracellular membrane-associated marker. Then, Rose Bengal (RB), a photoactivable drug characterized by a relatively low cellular uptake, was incorporated into nascent glioblastoma-derived M-NVs and finally administered to homotypic receiving cells, showing an increased degree of internalization as well as induced cytotoxic effects, even in the absence of photodynamic direct stimulation. Similar results were also obtained assaying lyophilized M-NVs loaded with RB. In conclusion, M-NVs generated by cell membranes effectively deliver several cargoes, including therapeutic molecules, maintain functionality after lyophilization, and show significant internalization effects, making them a promising strategy for therapeutic applications against human glioblastoma cells.
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Affiliation(s)
- Martina Massarotti
- Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy; (M.M.); (A.M.); (G.M.); (C.C.)
| | - Paola Corna
- Department of Clinical Surgical Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy; (P.C.); (L.M.)
| | - Aromita Mallik
- Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy; (M.M.); (A.M.); (G.M.); (C.C.)
| | - Gloria Milanesi
- Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy; (M.M.); (A.M.); (G.M.); (C.C.)
| | - Claudio Casali
- Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy; (M.M.); (A.M.); (G.M.); (C.C.)
| | - Lorenzo Magrassi
- Department of Clinical Surgical Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy; (P.C.); (L.M.)
| | - Sergio Comincini
- Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy; (M.M.); (A.M.); (G.M.); (C.C.)
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24
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Völlmecke K, Kramer M, Horky C, Dückmann O, Mulac D, Langer K, Kuckling D. Self-immolative polydisulfides and their use as nanoparticles for drug delivery systems. RSC Adv 2024; 14:35568-35577. [PMID: 39512642 PMCID: PMC11541933 DOI: 10.1039/d4ra07228f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 10/31/2024] [Indexed: 11/15/2024] Open
Abstract
Over the last few decades, nanotechnology has established to be a promising field in medicine. A remaining dominant challenge in today's pharmacotherapy is the limited selectivity of active pharmaceutical ingredients and associated undesirable side effects. Controlled drug release can be promoted by smart drug delivery systems, which release embedded API primarily depending on specific stimuli. Consequently, also the microenvironment of tumor tissue can be used advantageously. Dithiothreitol (DTT) based self-immolative polydisulfides were synthesized that preferentially respond to pathologically increased glutathione (GSH) concentrations, as found in solid tumors. The synthesis with different degrees of polymerisation was investigated as well as the synthesis of a copolymer consisting of dithiothreitol and butanedithiol (BDT). Toxicity tests were carried out on pure polymers and their degradation products. The ability to degrade was examined at pathological and physiological glutathione concentrations in order to test the suitability of the polymer as a matrix for nanoparticulate carrier systems. In addition, the processability of one polymer into nanoparticles was investigated as well as the degradation behaviour with glutathione.
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Affiliation(s)
| | - Maurice Kramer
- Institute of Pharmaceutical Technology and Biopharmacy, University of Münster Corrensstr. 48 D-48149 Münster Germany
| | - Corinna Horky
- Institute of Pharmaceutical Technology and Biopharmacy, University of Münster Corrensstr. 48 D-48149 Münster Germany
| | - Oliver Dückmann
- Paderborn University Warburger Straße 100 33098 Paderborn Germany
| | - Dennis Mulac
- Institute of Pharmaceutical Technology and Biopharmacy, University of Münster Corrensstr. 48 D-48149 Münster Germany
| | - Klaus Langer
- Institute of Pharmaceutical Technology and Biopharmacy, University of Münster Corrensstr. 48 D-48149 Münster Germany
| | - Dirk Kuckling
- Paderborn University Warburger Straße 100 33098 Paderborn Germany
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25
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Lai MH, Lin WJ. Zein-PEG nanoparticles modified with hyaluronic acid for paclitaxel delivery in SKOV3 ovarian cancer cells. Int J Biol Macromol 2024; 281:136651. [PMID: 39423978 DOI: 10.1016/j.ijbiomac.2024.136651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Revised: 09/30/2024] [Accepted: 10/15/2024] [Indexed: 10/21/2024]
Abstract
Ovarian cancer is a leading gynecological cancer globally. This study aimed to develop hyaluronic acid-modified polyethylene glycol conjugated zein nanoparticles (zein-PEG/HA NPs) to enhance paclitaxel (PTX) cytotoxicity in SKOV3 ovarian cancer cells. Zein-PEG, with its amphiphilic nature, self-assembled into micelles to encapsulate the hydrophobic PTX, while the PEG shell retained micelle stability and hemolytic resistance. PTX@zein-PEG micelles (17.2 ± 0.3 mV) were complexed with negatively charged HA through electrostatic interactions, resulting in PTX@zein-PEG/HA NPs with a negative zeta potential of -15.3 ± 1.1 mV. Cellular uptake of fluorescent zein-PEG/HA NPs was higher than zein-PEG micelles in CD44-overexpressing SKOV3 cells. Additionally, PTX@zein-PEG/HA NPs demonstrated significantly greater cytotoxicity than free PTX and PTX@zein-PEG micelles, with IC50 values reduced by 6.13-fold and 3.58-fold, respectively. PTX@zein-PEG/HA NPs induced the highest expression levels of apoptotic proteins, particularly PARP, in SKOV3 cells compared to PTX@zein-PEG NPs and free PTX. In summary, PTX@zein-PEG/HA NPs demonstrated potential as a delivery system for PTX in ovarian cancer.
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Affiliation(s)
- Min-Hua Lai
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10050, Taiwan
| | - Wen Jen Lin
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10050, Taiwan; Drug Research Center, College of Medicine, National Taiwan University, Taipei 10050, Taiwan.
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26
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Ye G, Luo S, Zafar H, Ge H, Liu B, Wang N, Jin Y, Wang M, Chen X, Ye X. pH-sensitive supramolecular self-assembled peptide hydrogel for the treatment of esophageal cancer. Front Pharmacol 2024; 15:1453422. [PMID: 39512832 PMCID: PMC11540713 DOI: 10.3389/fphar.2024.1453422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Accepted: 10/07/2024] [Indexed: 11/15/2024] Open
Abstract
Esophageal cancer is one of the most common cancers in the world, ranking sixth in cancer-related mortality. Doxorubicin (DOX), as a classic broad-spectrum, non-specific small-molecular anti-tumor drug, has achieved widespread use, including in the treatment of esophageal cancer. However, due to its strong cardiotoxicity, poor tumor-targeting ability, and short half-life, the clinical application of DOX has been greatly limited. In this research, we designed and successfully synthesized a peptide sequence IEIIIK (IEK for short) with excellent pH responsiveness. Under physiological conditions (pH 7.4), the peptide can encapsulate DOX and self-assemble into a stable hydrogel (DOX-IEK) through hydrophobic and electrostatic interactions. After being injected into the acidic tumor microenvironment, the protonation degree of alkaline amino acid lysine increased and the negative charge of glutamate decreased, directly leading to enhanced electrostatic repulsion and subsequent hydrogel dissociation. Released DOX can accumulate in tumor tissue and achieve anti-tumor efficacy. More importantly, the hydrogel can act as a drug reservoir for sustained drug release, improving the drug targeting ability, prolonging the duration of drug administration to compensate for the short half-life of DOX, and reducing systemic toxicity. Ideal anti-tumor efficacy has been achieved in both the in vitro and in vivo experiments.
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Affiliation(s)
- Gaobing Ye
- Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Shiyao Luo
- State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Hajra Zafar
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - Honglei Ge
- Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Binbin Liu
- State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Nan Wang
- State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Yu Jin
- State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Miao Wang
- State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Xu Chen
- Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiaoming Ye
- Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
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27
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Li Y, Li M, Zheng J, Ma Z, Yu T, Zhu Y, Li P, Nie F. Ultrasound-Responsive Nanocarriers Delivering siRNA and Fe 3O 4 Nanoparticles Reprogram Macrophages and Inhibit M2 Polarization for Enhanced NSCLC Immunotherapy. ACS APPLIED MATERIALS & INTERFACES 2024; 16:56634-56652. [PMID: 39378273 DOI: 10.1021/acsami.4c10036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/10/2024]
Abstract
Lung cancer has emerged as the second most common type of malignant tumor worldwide, and it has the highest mortality rate. The overall 5-year survival rate stands at less than 20%, which is primarily related to the limited therapeutic options and the complexity of the tumor immune microenvironment. In the tumor microenvironment, M1 macrophages are known for their tumor-killing capabilities. Although they are less numerous, they play an important role in tumor immunity. Therefore, increasing M1 macrophages' presence is considered a strategy to enhance targeted phagocytosis and antitumor efficacy in nonsmall cell lung cancer (NSCLC). This study introduces the development of folic acid (FA)-conjugated liposomal nanobubbles for precise delivery of PFH, STAT3 siRNA, and Fe3O4 to the tumor microenvironment. These encapsulated PFH liposomal nanobubbles exhibit significant visualization potential and underwent phase transition when exposed to low-intensity focused ultrasound (LIFU). The release of Fe3O4 activates the IRF5 signaling pathway, converting M2-like macrophages to M1. In addition, STAT3 siRNA effectively interrupts the JAK-STAT3 pathway, inhibiting the polarization of M2-like macrophages in tumor-associated macrophages (TAMs). This dual-action therapy facilitates T-cell activation and proliferation, thereby enhancing the immune response against NSCLC.
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Affiliation(s)
- Yuanyuan Li
- Ultrasound Medical Center, Gansu Province Clinical Research Center for Ultrasonography, Gansu Province Medical Engineering Research Center for Intelligence Ultrasound, Lanzhou University Second Hospital, Lanzhou 730000, China
| | - Ming Li
- Ultrasound Medical Center, Gansu Province Clinical Research Center for Ultrasonography, Gansu Province Medical Engineering Research Center for Intelligence Ultrasound, Lanzhou University Second Hospital, Lanzhou 730000, China
| | - Jun Zheng
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People's Republic of China
| | - Zhen Ma
- Peking University Third Hospital, Beijing 100191, China
| | - Tingting Yu
- Ultrasound Medical Center, Gansu Province Clinical Research Center for Ultrasonography, Gansu Province Medical Engineering Research Center for Intelligence Ultrasound, Lanzhou University Second Hospital, Lanzhou 730000, China
| | - Yangyang Zhu
- Ultrasound Medical Center, Gansu Province Clinical Research Center for Ultrasonography, Gansu Province Medical Engineering Research Center for Intelligence Ultrasound, Lanzhou University Second Hospital, Lanzhou 730000, China
| | - Pan Li
- The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People's Republic of China
| | - Fang Nie
- Ultrasound Medical Center, Gansu Province Clinical Research Center for Ultrasonography, Gansu Province Medical Engineering Research Center for Intelligence Ultrasound, Lanzhou University Second Hospital, Lanzhou 730000, China
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28
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Taghizadeh-Tabarsi R, Akbari-Birgani S, Amjadi M, Mohammadi S, Nikfarjam N, Kusamori K. Aptamer-guided graphene oxide quantum dots for targeted suicide gene therapy in an organoid model of luminal breast cancer. Sci Rep 2024; 14:24104. [PMID: 39406784 PMCID: PMC11480468 DOI: 10.1038/s41598-024-74312-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 09/25/2024] [Indexed: 10/19/2024] Open
Abstract
Breast cancer is one of the most common cancers in women. One of the best therapeutic methods against breast cancer is gene therapy, while having an appropriate gene carrier is the biggest challenge of gene therapy. Hence, developing carriers with low cytotoxicity and high gene transfection efficiency, and preferentially with the selective function of gene delivery is a critical demand for this method. In the present study, we introduce a novel targeted carrier to deliver the inducible caspase-9 suicide gene (pLVSIN-iC9) into breast cancer cells. The carrier is composed of graphene oxide quantum dots decorated with polyethyleneimine, and S2.2; an aptamer with high affinity to MUC1 (GOQD-PEI/S2.2). Due to the overexpression of MUC1 in breast cancer cells, the designed GOQD-PEI/S2.2/pLVSIN-iC9 can selectively target cancer cells. Moreover, to better mimic solid tumor conditions, and to evaluate the selective effect of the GOQD-PEI/S2.2/pLVSIN-iC9, an organoid model derived from human dermal fibroblasts (HDF) and MCF-7 cells (coculture organoid) was generated and characterized. The results demonstrate that the coculture organoid model adapts the tissue structure of luminal breast cancer, as well. Therefore, the organoids were subjected to treatment with targeted gene therapy using GOQD-PEI/S2.2/pLVSIN-iC9. Our evidence supports the targeted killing effect of iC9 on the breast cancer cells of the organoids and suggests the good potential of the newly introduced carriers in targeted gene delivery.
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Affiliation(s)
- Reza Taghizadeh-Tabarsi
- Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, 4513766731, Iran
| | - Shiva Akbari-Birgani
- Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, 4513766731, Iran.
- Research Center for Basic Sciences and Modern Technologies (RBST), Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran.
| | - Mehrnaz Amjadi
- Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, 4513766731, Iran
| | - Soheila Mohammadi
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Nasser Nikfarjam
- Department of Chemical Engineering, College of Engineering and Computing, University of South Carolina, Columbia, SC, 29208, USA
- Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, 4513766731, Iran
| | - Kosuke Kusamori
- Laboratory of Cellular Drug Discovery and Development, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
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Honfroy A, Bertouille J, Turea AM, Cauwenbergh T, Bridoux J, Lensen N, Mangialetto J, Van den Brande N, White JF, Gardiner J, Brigaud T, Ballet S, Hernot S, Chaume G, Martin C. Fluorinated Peptide Hydrogels Result in Longer In Vivo Residence Time after Subcutaneous Administration. Biomacromolecules 2024; 25:6666-6680. [PMID: 39230056 DOI: 10.1021/acs.biomac.4c00872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2024]
Abstract
Peptide-based hydrogels are of interest to biomedical applications. Herein, we have explored the introduction of fluorinated amino acids in hydrogelator H-FQFQFK-NH2 (P1) to design a series of fluorinated peptide hydrogels and evaluate the in vitro and in vivo properties of the most promising analogues. The impact of fluorinated groups on peptide gelation, secondary structure, and self-assembly processes was assessed. We show that fluorine can significantly improve hydrogel stiffness, compared to the nonfluorinated reference P1. For P15 (H-FQFQF(o-CF3)K-NH2), P18 (H-FQFQF(F5)K-NH2), and P19 (H-FQFQM(CF3)K-NH2), microscopy studies scrutinized fiber morphologies and alignment in the network. In vitro release studies of hydrogels loaded with an opioid cargo suggested improved hydrogel stability for P15 and P18. This improved stability was further validated in vivo, notably for P15, giving the most significant increased gel residence time, with more than 20% of hydrogel still present 9 days post-injection, as monitored by nuclear SPECT-CT imaging.
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Affiliation(s)
- Aurélie Honfroy
- Research Group of Organic Chemistry (ORGC), Vrije Universiteit Brussel, Pleinlaan 2, Brussels B-1050, Belgium
- VUB, Molecular Imaging and Therapy Research Group (MITH), Laarbeeklaan 103, Jette 1090, Belgium
- CY Cergy Paris Université, CNRS, BioCIS UMR 8076, Cergy-Pontoise 95000, France
- Université Paris-Saclay, CNRS, BioCIS UMR 8076, Orsay 91400, France
| | - Jolien Bertouille
- Research Group of Organic Chemistry (ORGC), Vrije Universiteit Brussel, Pleinlaan 2, Brussels B-1050, Belgium
| | - Ana-Maria Turea
- Research Group of Organic Chemistry (ORGC), Vrije Universiteit Brussel, Pleinlaan 2, Brussels B-1050, Belgium
| | - Thibault Cauwenbergh
- Research Group of Organic Chemistry (ORGC), Vrije Universiteit Brussel, Pleinlaan 2, Brussels B-1050, Belgium
| | - Jessica Bridoux
- VUB, Molecular Imaging and Therapy Research Group (MITH), Laarbeeklaan 103, Jette 1090, Belgium
| | - Nathalie Lensen
- CY Cergy Paris Université, CNRS, BioCIS UMR 8076, Cergy-Pontoise 95000, France
- Université Paris-Saclay, CNRS, BioCIS UMR 8076, Orsay 91400, France
| | - Jessica Mangialetto
- Research Group Sustainable Materials Engineering (SUME), Lab of Physical Chemistry and Polymer Science (FYSC), Vrije Universiteit Brussel, Pleinlaan 2, Brussels B-1050, Belgium
| | - Niko Van den Brande
- Research Group Sustainable Materials Engineering (SUME), Lab of Physical Chemistry and Polymer Science (FYSC), Vrije Universiteit Brussel, Pleinlaan 2, Brussels B-1050, Belgium
| | - Jacinta F White
- CSIRO Manufacturing, Bayview Avenue, Clayton, VIC 3169, Australia
| | - James Gardiner
- CSIRO Manufacturing, Bayview Avenue, Clayton, VIC 3169, Australia
| | - Thierry Brigaud
- CY Cergy Paris Université, CNRS, BioCIS UMR 8076, Cergy-Pontoise 95000, France
- Université Paris-Saclay, CNRS, BioCIS UMR 8076, Orsay 91400, France
| | - Steven Ballet
- Research Group of Organic Chemistry (ORGC), Vrije Universiteit Brussel, Pleinlaan 2, Brussels B-1050, Belgium
| | - Sophie Hernot
- VUB, Molecular Imaging and Therapy Research Group (MITH), Laarbeeklaan 103, Jette 1090, Belgium
| | - Grégory Chaume
- CY Cergy Paris Université, CNRS, BioCIS UMR 8076, Cergy-Pontoise 95000, France
- Université Paris-Saclay, CNRS, BioCIS UMR 8076, Orsay 91400, France
| | - Charlotte Martin
- Research Group of Organic Chemistry (ORGC), Vrije Universiteit Brussel, Pleinlaan 2, Brussels B-1050, Belgium
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30
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Don TM, Hong YT, Jheng PR, Chuang EY, Huang YC. Improved camptothecin encapsulation and efficacy by environmentally sensitive block copolymer/chitosan/fucoidan nanoparticles for targeting lung cancer cells. Int J Biol Macromol 2024; 277:133901. [PMID: 39038585 DOI: 10.1016/j.ijbiomac.2024.133901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 07/11/2024] [Accepted: 07/13/2024] [Indexed: 07/24/2024]
Abstract
In this study, thermo-sensitive poly(N-isopropyl acrylamide) (PNP) was polymerized with pH-sensitive poly(acrylic acid) (PAA) to prepare a PAA-b-PNP block copolymer. Above its cloud point, the block copolymer self-assembled into nanoparticles (NPs), encapsulating the anticancer drug camptothecin (CPT) in situ. Chitosan (CS) and fucoidan (Fu) further modified these NPs, forming Fu-CPT-NPs to enhance biocompatibility, drug encapsulation efficiency (EE), and loading content (LC), crucially facilitating P-selectin targeting of lung cancer cells through a drug delivery system. The EE and LC reached 82 % and 3.5 %, respectively. According to transmission electron microscope observation, these Fu-CPT-NPs had uniform spherical shapes with an average diameter of ca. 250 nm. They could maintain their stability in a pH range of 5.0-6.8. In vitro experimental results revealed that the Fu-CPT-NPs exhibited good biocompatibility and had anticancer activity after encapsulating CPT. It could deliver CPT to cancer cells by targeting P-selectin, effectively increasing cell uptake and inducing cell apoptosis. Animal study results showed that the Fu-CPT-NPs inhibited lung tumor growth by increasing tumor cell apoptosis without causing significant tissue damage related to generating reactive oxygen species in lung cancer cells. This system can effectively improve drug-delivery efficiency and treatment effects and has great potential for treating lung cancer.
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Affiliation(s)
- Trong-Ming Don
- Department of Chemical and Materials Engineering, Tamkang University, New Taipei City, Taiwan
| | - Yu-Ting Hong
- College of Life Sciences, Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan
| | - Pei-Ru Jheng
- Graduate Institute of Biomedical Materials and Tissue Engineering, International PhD Program in Biomedical Engineering, Taipei Medical University, Taipei, Taiwan
| | - Er-Yuan Chuang
- Graduate Institute of Biomedical Materials and Tissue Engineering, International PhD Program in Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; Cell Physiology and Molecular Image Research Center, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.
| | - Yi-Cheng Huang
- College of Life Sciences, Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan.
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Shin S, Jo H, Agura T, Jeong S, Ahn H, Kim Y, Kang JS. Use of surface-modified porous silicon nanoparticles to deliver temozolomide with enhanced pharmacokinetic and therapeutic efficacy for intracranial glioblastoma in mice. J Mater Chem B 2024; 12:9335-9344. [PMID: 39171683 DOI: 10.1039/d4tb00631c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/23/2024]
Abstract
Glioblastoma (GBM) is one of the most common and fatal primary brain tumors, with a 5-year survival rate of 7.2%. The standard treatment for GBM involves surgical resection followed by chemoradiotherapy, and temozolomide (TMZ) is currently the only approved chemotherapeutic agent for the treatment of GBM. However, hydrolytic instability and insufficient drug accumulation are major challenges that limit the effectiveness of TMZ chemotherapy. To overcome these limitations, we have developed a drug delivery platform utilizing porous silicon nanoparticles (pSiNPs) to improve the stability and blood-brain barrier penetration of TMZ. The pSiNPs are synthesized via electrochemical etching and functionalized with octadecane. The octadecyl-modified pSiNP (pSiNP-C18) demonstrates the superiority of loading efficiency, in vivo stability, and brain accumulation of TMZ. Treatment of intracranial tumor-bearing mice with TMZ-loaded pSiNP-C18 results in a decreased tumor burden and a corresponding increase in survival compared with equivalent free-drug dosing. Furthermore, the mice treated with TMZ-loaded nanoparticles do not exhibit in vivo toxicity, thus underscoring the preclinical potential of the pSiNP-based platform for the delivery of therapeutic agents to gliomas.
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Affiliation(s)
- Seulgi Shin
- Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
- Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul 03080, Republic of Korea
- Department of Research and Development, N therapeutics Co., Ltd, Seoul 08813, Republic of Korea
| | - Hyejung Jo
- Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
| | - Tomoyo Agura
- Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
| | - Seoyoun Jeong
- Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
| | - Hyovin Ahn
- Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
| | - Yejin Kim
- Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
- Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul 03080, Republic of Korea
| | - Jae Seung Kang
- Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
- Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul 03080, Republic of Korea
- Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea
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Soroushmanesh M, Dinari M, Farrokhpour H. Comprehensive Computational Investigation of the Porphyrin-Based COF as a Nanocarrier for Delivering Anti-Cancer Drugs: A Combined MD Simulation and DFT Calculation. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2024; 40:19073-19085. [PMID: 39189806 DOI: 10.1021/acs.langmuir.4c02154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/28/2024]
Abstract
As nanomaterials have gained prominence in drug delivery technology, exploring their feasibility through computational methods is beneficial before practical tests. In this study, we aim to evaluate the capability of the porphyrin-based covalent organic framework COF-366 as a nanocarrier for two anticancer drugs, irinotecan (IRI) and doxorubicin (DOX). The optimal binding conformation of the drug molecules on the COF surface was predicted by using molecular docking. Subsequently, molecular dynamic simulation (MD) was performed to assess the adsorption mechanism of drug molecules on the COF in the aqueous environment. The free energy of adsorption for DOX and IRI was estimated to be -20.07 and -23.89 kcal/mol, respectively. The adsorption of both drugs on the COF surface is mainly influenced by the π-π interaction. Furthermore, density functional theory (DFT) calculation, natural bond orbital (NBO), and quantum theory of atoms in molecules (QTAIM) analyses were employed to investigate the structural stability of Drug@COF complexes and gain a detailed understanding of the interaction between them at the molecular level. Based on DFT results, it was found that in addition to π-π interaction, the bis-piperidine-phenylene interaction affects the adsorption of IRI on the COF surface. Moreover, the diffusion behavior of the drug molecule inside the COF pore was simulated using a ten-layer COF. Based on the mean square displacement analysis, the diffusion coefficients of DOX and IRI within the COF pore were calculated to be 108 and 97 um2/s, respectively. This computational study sheds light on how different types of interactions between the drug molecule and COF affect the adsorption and diffusion process. Our findings validated that the porphyrin-based COF-366 can serve as a nanobased platform for delivering DOX and IRI.
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Affiliation(s)
- Mohsen Soroushmanesh
- Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111, Islamic Republic of Iran
| | - Mohammad Dinari
- Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111, Islamic Republic of Iran
| | - Hossein Farrokhpour
- Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111, Islamic Republic of Iran
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Sadri M, Heidari S, Faridzadeh A, Roozbehani M, Toosi S, Mahmoudian RA, Hoseinzadeh A, Salmani Fard MT, Arab FL, Fard SR, Faraji F. Potential applications of macrophages in cancer immunotherapy. Biomed Pharmacother 2024; 178:117161. [PMID: 39047419 DOI: 10.1016/j.biopha.2024.117161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 07/02/2024] [Accepted: 07/15/2024] [Indexed: 07/27/2024] Open
Abstract
Immunotherapy has improved cancer treatment based on investigations of tumor immune escape. Manipulation of the immune system stimulates antitumor immune responses and blocks tumor immune escape routes. Genetically adoptive cell therapy, such as T cells, has yielded promising results for hematologic malignancies, but their application to solid tumors has been challenging. Macrophages have a wide broad of capabilities in regulating immune responses, homeostasis, and tissue development, as well as the ability to phagocyte, present antigens, and infiltrate the tumor microenvironment (TME). Given the importance of macrophages in cancer development, they could serve as novel tool for tumor treatment. Therefore, macrophages are used in different formats for direct and indirect targeting of tumor cells. This review summarized the available data on the various applications of macrophages in cancer immunotherapy.
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Affiliation(s)
- Maryam Sadri
- Department of Immunology, Iran University of Medical Sciences, Shahid Hemmat Highway, P.O. Box: 1449614535, Tehran, Iran.
| | - Sahel Heidari
- Department of Immunology, Iran University of Medical Sciences, Shahid Hemmat Highway, P.O. Box: 1449614535, Tehran, Iran.
| | - Arezoo Faridzadeh
- Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad 1313199137, Iran.
| | - Mona Roozbehani
- Vaccine Research Center, Iran University of Medical Sciences, Shahid Hemmat Highway, P.O. Box: 1449614535, Tehran, Iran.
| | - Shirin Toosi
- Stem Cell and Regenerative Medicine Center, Mashhad University of Medical Science, Mashhad 1313199137, Iran.
| | | | - Akram Hoseinzadeh
- Department of Immunology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan 3513119111, Iran.
| | - Mohammad Taha Salmani Fard
- School of Biology, College of Science, University of Tehran, Faculty of Sciences, Enqelab Square, Tehran 1417614411, Iran.
| | - Fahimeh Lavi Arab
- Immunology Research center, Mashhad University of Medical Sciences, Mashhad 1313199137, Iran.
| | - Soheil Rahmani Fard
- Antimicrobial Resistance Research Center, Institute of Immunology and Infection Diseases Iran University of Medical Sciences, Floor 3, Building no. 3, Hazrat-e Rasool General Hospital, Niyayesh St, Sattar Khan St, P.O. Box: 1445613131, Tehran, Iran.
| | - Fatemeh Faraji
- Antimicrobial Resistance Research Center, Institute of Immunology and Infection Diseases Iran University of Medical Sciences, Floor 3, Building no. 3, Hazrat-e Rasool General Hospital, Niyayesh St, Sattar Khan St, P.O. Box: 1445613131, Tehran, Iran.
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34
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Laha A, Nasra S, Bhatia D, Kumar A. Advancements in rheumatoid arthritis therapy: a journey from conventional therapy to precision medicine via nanoparticles targeting immune cells. NANOSCALE 2024; 16:14975-14993. [PMID: 39056352 DOI: 10.1039/d4nr02182g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
Rheumatoid arthritis (RA) is a progressive autoimmune disease that mainly affects the inner lining of the synovial joints and leads to chronic inflammation. While RA is not known as lethal, recent research indicates that it may be a silent killer because of its strong association with an increased risk of chronic lung and heart diseases. Patients develop these systemic consequences due to the regular uptake of heavy drugs such as disease-modifying antirheumatic medications (DMARDs), glucocorticoids (GCs), nonsteroidal anti-inflammatory medicines (NSAIDs), etc. Nevertheless, a number of these medications have off-target effects, which might cause adverse toxicity, and have started to become resistant in patients as well. Therefore, alternative and promising therapeutic techniques must be explored and adopted, such as post-translational modification inhibitors (like protein arginine deiminase inhibitors), RNA interference by siRNA, epigenetic drugs, peptide therapy, etc., specifically in macrophages, neutrophils, Treg cells and dendritic cells (DCs). As the target cells are specific, ensuring targeted delivery is also equally important, which can be achieved with the advent of nanotechnology. Furthermore, these nanocarriers have fewer off-site side effects, enable drug combinations, and allow for lower drug dosages. Among the nanoparticles that can be used for targeting, there are both inorganic and organic nanomaterials such as solid-lipid nanoparticles, liposomes, hydrogels, dendrimers, and biomimetics that have been discussed. This review highlights contemporary therapy options targeting macrophages, neutrophils, Treg cells, and DCs and explores the application of diverse nanotechnological techniques to enhance precision RA therapies.
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Affiliation(s)
- Anwesha Laha
- Biological and Life Sciences, School of Arts & Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad 380009, Gujarat, India.
| | - Simran Nasra
- Biological and Life Sciences, School of Arts & Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad 380009, Gujarat, India.
| | - Dhiraj Bhatia
- Indian Institute of Technology Gandhinagar, Palaj, Gandhinagar - 382055, Gujarat, India
| | - Ashutosh Kumar
- Biological and Life Sciences, School of Arts & Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad 380009, Gujarat, India.
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35
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Iureva AM, Nikitin PI, Tereshina ED, Nikitin MP, Shipunova VO. The influence of various polymer coatings on the in vitro and in vivo properties of PLGA nanoparticles: Comprehensive study. Eur J Pharm Biopharm 2024; 201:114366. [PMID: 38876361 DOI: 10.1016/j.ejpb.2024.114366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Revised: 06/03/2024] [Accepted: 06/11/2024] [Indexed: 06/16/2024]
Abstract
Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) with various surface chemistry are widely used in biomedicine for theranostic applications. The nature of the external coating of nanoparticles has a significant influence on their efficiency as drug carriers or visualization agents. However, information about the mechanisms of nanoparticle accumulation in tumors and the influence of their surface properties on biodistribution is scarce due to the lack of systematic evaluation. Here we investigate the effect of different polymer coatings of the surface on in vitro and in vivo properties of PLGA nanoparticles. Namely, cell binding efficiency, cytotoxicity, efficiency of fluorescent bioimaging, and tumor accumulation were tested. The highest binding efficiency in vitro and cytotoxicity were observed for positively charged polymers. Interestingly, in vivo fluorescent visualization of tumor-bearing mice and quantitative measurements of biodistribution of magnetite-loaded nanoparticles indicated different dependences of accumulation in tumors on the coating of PLGA nanoparticles. This means that nanoparticle surface properties can simultaneously enhance imaging efficiency and decrease quantitative accumulation in tumors. The obtained data demonstrate the complexity of the dependence of nanoparticles' effectiveness for theranostic applications on surface features. We believe that this study will contribute to the rational design of nanoparticles for effective cancer diagnostics and therapy.
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Affiliation(s)
- Anna M Iureva
- Moscow Institute of Physics and Technology, 9 Institutskiy Per., 141701 Dolgoprudny, Russia
| | - Petr I Nikitin
- Prokhorov General Physics Institute, Russian Academy of Sciences, 38 Vavilov Street, 119991 Moscow, Russia
| | - Ekaterina D Tereshina
- Moscow Institute of Physics and Technology, 9 Institutskiy Per., 141701 Dolgoprudny, Russia
| | - Maxim P Nikitin
- Moscow Institute of Physics and Technology, 9 Institutskiy Per., 141701 Dolgoprudny, Russia; Nanobiomedicine Division, Sirius University of Science and Technology, 1 Olympic Ave., 354340 Sochi, Russia
| | - Victoria O Shipunova
- Moscow Institute of Physics and Technology, 9 Institutskiy Per., 141701 Dolgoprudny, Russia; Nanobiomedicine Division, Sirius University of Science and Technology, 1 Olympic Ave., 354340 Sochi, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya St., 117997 Moscow, Russia.
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36
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Kamali M, Jafari H, Taati F, Mohammadnejad J, Daemi A. Synthesis of chitosan polyethylene glycol antibody complex for delivery of Imatinib in lung cancer cell lines. J Biochem Mol Toxicol 2024; 38:e23787. [PMID: 39072816 DOI: 10.1002/jbt.23787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 03/21/2024] [Accepted: 07/18/2024] [Indexed: 07/30/2024]
Abstract
Lung cancer is known as the most common cancer. Although the Ramucirumab antibody is a second-line treatment for lung cancer, the high interstitial fluid pressure limits the antibody's performance. In this way, Imatinib is a chemotherapeutic drug to reduce the interstitial fluid pressure. Up to now, unfortunately, both Ramucirumab and imatinib have not been reported in one nanosystem for cancer therapy. To fulfill this shortcoming, this paper aims to design a chitosan nanocarrier that loads imatinib and attaches to Ramucirumab for selective bonding to A549. Therefore, this paper aims to develop a polymeric nanosystem for non-small cell lung cancer (NSCLC) treatment. In first, the chitosan polyethylene glycol nanoparticle is synthesized, loaded with imatinib, and then targeted using Ramucirumab. Afterwards, the CS-PEG-Ab-Im by FTIR, TEM, DLS, zeta potential, and TGA techniques are characterized. The size of CS-PEG-Ab-Im was 25-30 nm, its surface charge was 13.1 mV, and the shape of CS-PEG-Ab-Im was nearly spherical and cylindrical. The therapeutic potential of CS-PEG-Ab-Im was assessed using the A549 cell line. According to the obtained results, the cell viability was 48% after 48 h of treatment of A549 cells using the IC50 concentration of CS-PEG-Ab-Im (100 nanomolar). Moreover, the apoptosis and cell cycle arrest percentages were increased by 3 and 6 times, respectively, as compared to free imatinib. Furthermore, the release rate of imatinib from CS-PEG-Ab-Im in an acidic medium was 17% during 1 h, indicating five times the imatinib release in the natural medium. Eventually, the result of flow cytometry indicates the more apoptotic effect of nanosystem to free imatinib and CS-PEG-Ab. Besides, cell arresting result exhibits the CS-PEG-Ab-Im and causes cell arrested at G1 by %8.17. Thus, it can be concluded that CS-PEG-Ab-Im can be an ideal nanosystem in NSCLC treatment.
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Affiliation(s)
- Mehrdad Kamali
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Hanieh Jafari
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Fatemeh Taati
- Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
| | - Javad Mohammadnejad
- Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
| | - Amin Daemi
- Department of Medical Biochemistry, Faculty of Medicine, Cukurova University, Adana, Turkey
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Jahanafrooz Z, Oroojalian F, Mokhtarzadeh A, Rahdar A, Díez-Pascual AM. Nanovaccines: Immunogenic tumor antigens, targeted delivery, and combination therapy to enhance cancer immunotherapy. Drug Dev Res 2024; 85:e22244. [PMID: 39138855 DOI: 10.1002/ddr.22244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 04/16/2024] [Accepted: 07/29/2024] [Indexed: 08/15/2024]
Abstract
Nanovaccines have been designed to overcome the limitations associated with conventional vaccines. Effective delivery methods such as engineered carriers or smart nanoparticles (NPs) are critical requisites for inducing self-tolerance and optimizing vaccine immunogenicity with minimum side effects. NPs can be used as adjuvants, immunogens, or nanocarriers to develop nanovaccines for efficient antigen delivery. Multiloaded nanovaccines carrying multiple tumor antigens along with immunostimulants can effectively increase immunity against tumor cells. They can be biologically engineered to boost interactions with dendritic cells and to allow a gradual and constant antigen release. Modifying NPs surface properties, using high-density lipoprotein-mimicking nanodiscs, and developing nano-based artificial antigen-presenting cells such as dendritic cell-derived-exosomes are amongst the new developed technologies to enhance antigen-presentation and immune reactions against tumor cells. The present review provides an overview on the different perspectives, improvements, and barriers of successful clinical application of current cancer therapeutic and vaccination options. The immunomodulatory effects of different types of nanovaccines and the nanoparticles incorporated into their structure are described. The advantages of using nanovaccines to prevent and treat common illnesses such as AIDS, malaria, cancer and tuberculosis are discussed. Further, potential paths to develop optimal cancer vaccines are described. Given the immunosuppressive characteristics of both cancer cells and the tumor microenvironment, applying immunomodulators and immune checkpoint inhibitors in combination with other conventional anticancer therapies are necessary to boost the effectiveness of the immune response.
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Affiliation(s)
- Zohreh Jahanafrooz
- Department of Biology, Faculty of Sciences, University of Maragheh, Maragheh, Iran
| | - Fatemeh Oroojalian
- Natural Products & Medicinal Plants Research Center, North Khorasan University of Medical Sciences Bojnurd, Bojnurd, Iran
- Department of Medical Nanotechnology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Ahad Mokhtarzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Abbas Rahdar
- Department of Physics, Faculty of Sciences, University of Zabol, Zabol, Iran
| | - Ana M Díez-Pascual
- Universidad de Alcalá, Facultad de Ciencias, Departamento de Química Analítica, Química Física e Ingenieria Química, Alcalá de Henares, Spain
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Ferrari G, Lopez-Martinez I, Wanek T, Kuntner C, Montagner D. Recent Advances on Pt-Based Compounds for Theranostic Applications. Molecules 2024; 29:3453. [PMID: 39124859 PMCID: PMC11313463 DOI: 10.3390/molecules29153453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 07/19/2024] [Accepted: 07/20/2024] [Indexed: 08/12/2024] Open
Abstract
Since the discovery of cisplatin's antitumoral activity and its approval as an anticancer drug, significant efforts have been made to enhance its physiological stability and anticancer efficacy and to reduce its side effects. With the rapid development of targeted and personalized therapies, and the promising theranostic approach, platinum drugs have found new opportunities in more sophisticated systems. Theranostic agents combine diagnostic and therapeutic moieties in one scaffold, enabling simultaneous disease monitoring, therapy delivery, response tracking, and treatment efficacy evaluation. In these systems, the platinum core serves as the therapeutic agent, while the functionalized ligand provides diagnostic tools using various imaging techniques. This review aims to highlight the significant role of platinum-based complexes in theranostic applications, and, to the best of our knowledge, this is the first focused contribution on this type of platinum compounds. This review presents a brief introduction to the development of platinum chemotherapeutic drugs, their limitations, and resistance mechanisms. It then describes recent advancements in integrating platinum complexes with diagnostic agents for both tumor treatment and monitoring. The main body is organized into three categories based on imaging techniques: fluorescence, positron emission tomography (PET), single-photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI). Finally, this review outlines promising strategies and future perspectives in this evolving field.
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Affiliation(s)
- Giulia Ferrari
- Department of Chemistry, Maynooth University, W23 F2H6 Maynooth, Ireland
| | - Ines Lopez-Martinez
- Division of Nuclear Medicine, Department of Biomedical Imaging and Image–Guided Therapy, Medical University of Vienna, 1090 Vienna, Austria
- Preclinical Imaging Lab (PIL), Department of Biomedical Imaging and Image–Guided Therapy, Medical University of Vienna, 1090 Vienna, Austria; (T.W.); (C.K.)
| | - Thomas Wanek
- Preclinical Imaging Lab (PIL), Department of Biomedical Imaging and Image–Guided Therapy, Medical University of Vienna, 1090 Vienna, Austria; (T.W.); (C.K.)
| | - Claudia Kuntner
- Preclinical Imaging Lab (PIL), Department of Biomedical Imaging and Image–Guided Therapy, Medical University of Vienna, 1090 Vienna, Austria; (T.W.); (C.K.)
- Medical Imaging Cluster (MIC), Medical University of Vienna, 1090 Vienna, Austria
| | - Diego Montagner
- Department of Chemistry, Maynooth University, W23 F2H6 Maynooth, Ireland
- Kathleen Londsdale Institute for Human Health Research, Maynooth University, W23 F2H6 Maynooth, Ireland
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Paul M, Das S, Ghosh B, Biswas S. Tocopherol-human serum albumin nanoparticles enhance lapatinib delivery and overcome doxorubicin resistance in breast cancer. Nanomedicine (Lond) 2024; 19:1431-1448. [PMID: 38953854 PMCID: PMC11318677 DOI: 10.1080/17435889.2024.2359357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 05/21/2024] [Indexed: 07/04/2024] Open
Abstract
Introduction: HER2, a tyrosine kinase receptor, is amplified in HER2-positive breast cancer, driving cell signaling and growth. Aim: This study aimed to combat multidrug resistance in Dox-insensitive breast adenocarcinoma by creating a nanoformulation therapy with a tyrosine kinase inhibitor. Methodology: Human serum albumin (HSA) was conjugated with α-D-tocopherol succinate to form nanoaggregates loaded with lapatinib (Lapa). Results: The resulting Lapa@HSA(VE) NPs were 117.2 nm in size and demonstrated IC50 values of 10.25 μg/ml on MCF7 (S) and 8.02 μg/ml on MCF7 (R) cell lines. Conclusion: Lapa@HSA(VE) NPs showed no hepatotoxicity, unlike free Lapa, as seen in acute toxicity studies in rats.
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Affiliation(s)
- Milan Paul
- Nanomedicine Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Medchal, Hyderabad500078, Telangana, India
| | - Sneha Das
- Nanomedicine Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Medchal, Hyderabad500078, Telangana, India
| | - Balaram Ghosh
- Nanomedicine Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Medchal, Hyderabad500078, Telangana, India
| | - Swati Biswas
- Nanomedicine Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Medchal, Hyderabad500078, Telangana, India
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40
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Wehn AC, Krestel E, Harapan BN, Klymchenko A, Plesnila N, Khalin I. To see or not to see: In vivo nanocarrier detection methods in the brain and their challenges. J Control Release 2024; 371:216-236. [PMID: 38810705 DOI: 10.1016/j.jconrel.2024.05.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 05/18/2024] [Accepted: 05/23/2024] [Indexed: 05/31/2024]
Abstract
Nanoparticles have a great potential to significantly improve the delivery of therapeutics to the brain and may also be equipped with properties to investigate brain function. The brain, being a highly complex organ shielded by selective barriers, requires its own specialized detection system. However, a significant hurdle to achieve these goals is still the identification of individual nanoparticles within the brain with sufficient cellular, subcellular, and temporal resolution. This review aims to provide a comprehensive summary of the current knowledge on detection systems for tracking nanoparticles across the blood-brain barrier and within the brain. We discuss commonly employed in vivo and ex vivo nanoparticle identification and quantification methods, as well as various imaging modalities able to detect nanoparticles in the brain. Advantages and weaknesses of these modalities as well as the biological factors that must be considered when interpreting results obtained through nanotechnologies are summarized. Finally, we critically evaluate the prevailing limitations of existing technologies and explore potential solutions.
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Affiliation(s)
- Antonia Clarissa Wehn
- Institute for Stroke and Dementia Research (ISD), Munich University Hospital, Feodor-Lynen-Straße 17, 81377, Germany; Department of Neurosurgery, University of Munich Medical Center, Marchioninistraße 17, 81377 Munich, Germany.
| | - Eva Krestel
- Institute for Stroke and Dementia Research (ISD), Munich University Hospital, Feodor-Lynen-Straße 17, 81377, Germany.
| | - Biyan Nathanael Harapan
- Institute for Stroke and Dementia Research (ISD), Munich University Hospital, Feodor-Lynen-Straße 17, 81377, Germany; Department of Neurosurgery, University of Munich Medical Center, Marchioninistraße 17, 81377 Munich, Germany.
| | - Andrey Klymchenko
- Laboratoire de Biophotonique et Pharmacologie, CNRS UMR 7213, Université de Strasbourg, 74 route du Rhin - CS 60024, 67401 Illkirch Cedex, France.
| | - Nikolaus Plesnila
- Institute for Stroke and Dementia Research (ISD), Munich University Hospital, Feodor-Lynen-Straße 17, 81377, Germany; Munich Cluster of Systems Neurology (SyNergy), Feodor-Lynen-Straße 17, 81377 Munich, Germany.
| | - Igor Khalin
- Institute for Stroke and Dementia Research (ISD), Munich University Hospital, Feodor-Lynen-Straße 17, 81377, Germany; Normandie University, UNICAEN, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), GIP Cyceron, Institute Blood and Brain @ Caen-Normandie (BB@C), 14 074 Bd Henri Becquerel, 14000 Caen, France.
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41
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Goto K, Ueno T, Sakaue S. Induction of antigen-specific immunity by mesoporous silica nanoparticles incorporating antigen peptides. J Biosci Bioeng 2024:S1389-1723(24)00161-0. [PMID: 38890051 DOI: 10.1016/j.jbiosc.2024.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 05/13/2024] [Accepted: 05/27/2024] [Indexed: 06/20/2024]
Abstract
Mesoporous silica nanoparticles (MSNs) are physically and chemically stable inorganic nanomaterials that have been attracting much attention as carriers for drug delivery systems in the field of nanomedicine. In the present study, we investigated the potential of MSN vaccines that incorporate antigen peptides for use in cancer immunotherapy. In vitro experiments demonstrated that fluorescently labeled MSNs accumulated in a line of mouse dendritic cells (DC2.4 cells), where the particles localized to the cytosol. These observations could suggest that MSNs have potential for use in delivering the loaded molecules into antigen-presenting cells, thereby stimulating the host acquired immune system. In vivo experiments demonstrated prolonged survival in mice implanted with ovalbumin (OVA)-expressing lymphoma cells (E.G7-OVA cells) following subcutaneous inoculation with MSNs incorporating OVA antigen peptides. Furthermore, OVA-specific immunoglobulin G antibodies and cytotoxic T lymphocytes were detected in the serum and the spleen cells, respectively, of mice inoculated with an MSN-OVA vaccine, indicating the induction of antigen-specific responses in both the humoral and cellular immune systems. These results suggested that the MSN therapies incorporating antigen peptides may serve as novel vaccines for cancer immunotherapy.
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Affiliation(s)
- Koichi Goto
- Division of Applied Life Sciences, Graduate School of Engineering, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
| | - Tomoya Ueno
- Division of Applied Life Sciences, Graduate School of Engineering, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan
| | - Saki Sakaue
- Division of Applied Life Sciences, Graduate School of Engineering, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan
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Hajjafari A, Sadr S, Rahdar A, Bayat M, Lotfalizadeh N, Dianaty S, Rezaei A, Moghaddam SP, Hajjafari K, Simab PA, Kharaba Z, Borji H, Pandey S. Exploring the integration of nanotechnology in the development and application of biosensors for enhanced detection and monitoring of colorectal cancer. INORG CHEM COMMUN 2024; 164:112409. [DOI: 10.1016/j.inoche.2024.112409] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/19/2024]
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43
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Mal S, Chakraborty S, Mahapatra M, Pakeeraiah K, Das S, Paidesetty SK, Roy P. Tackling breast cancer with gold nanoparticles: twinning synthesis and particle engineering with efficacy. NANOSCALE ADVANCES 2024; 6:2766-2812. [PMID: 38817429 PMCID: PMC11134266 DOI: 10.1039/d3na00988b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 04/10/2024] [Indexed: 06/01/2024]
Abstract
The World Health Organization identifies breast cancer as the most prevalent cancer despite predominantly affecting women. Surgery, hormonal therapy, chemotherapy, and radiation therapy are the current treatment modalities. Site-directed nanotherapeutics, engineered with multidimensional functionality are now the frontrunners in breast cancer diagnosis and treatment. Gold nanoparticles with their unique colloidal, optical, quantum, magnetic, mechanical, and electrical properties have become the most valuable weapon in this arsenal. Their advantages include facile modulation of shape and size, a high degree of reproducibility and stability, biocompatibility, and ease of particle engineering to induce multifunctionality. Additionally, the surface plasmon oscillation and high atomic number of gold provide distinct advantages for tailor-made diagnosis, therapy or theranostic applications in breast cancer such as photothermal therapy, radiotherapy, molecular labeling, imaging, and sensing. Although pre-clinical and clinical data are promising for nano-dimensional gold, their clinical translation is hampered by toxicity signs in major organs like the liver, kidneys and spleen. This has instigated global scientific brainstorming to explore feasible particle synthesis and engineering techniques to simultaneously improve the efficacy and versatility and widen the safety window of gold nanoparticles. The present work marks the first study on gold nanoparticle design and maneuvering techniques, elucidating their impact on the pharmacodynamics character and providing a clear-cut scientific roadmap for their fast-track entry into clinical practice.
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Affiliation(s)
- Suvadeep Mal
- Medicinal Chemistry Research Laboratory, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University) Campus-2, Ghatikia, Kalinga Nagar Bhubaneswar Odisha 751003 India
| | | | - Monalisa Mahapatra
- Medicinal Chemistry Research Laboratory, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University) Campus-2, Ghatikia, Kalinga Nagar Bhubaneswar Odisha 751003 India
| | - Kakarla Pakeeraiah
- Medicinal Chemistry Research Laboratory, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University) Campus-2, Ghatikia, Kalinga Nagar Bhubaneswar Odisha 751003 India
| | - Suvadra Das
- Basic Science and Humanities Department, University of Engineering and Management Action Area III, B/5, Newtown Kolkata West Bengal 700160 India
| | - Sudhir Kumar Paidesetty
- Medicinal Chemistry Research Laboratory, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University) Campus-2, Ghatikia, Kalinga Nagar Bhubaneswar Odisha 751003 India
| | - Partha Roy
- GITAM School of Pharmacy, GITAM (Deemed to be University) Vishakhapatnam 530045 India
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44
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Hristova-Panusheva K, Xenodochidis C, Georgieva M, Krasteva N. Nanoparticle-Mediated Drug Delivery Systems for Precision Targeting in Oncology. Pharmaceuticals (Basel) 2024; 17:677. [PMID: 38931344 PMCID: PMC11206252 DOI: 10.3390/ph17060677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 05/20/2024] [Accepted: 05/22/2024] [Indexed: 06/28/2024] Open
Abstract
Nanotechnology has emerged as a transformative force in oncology, facilitating advancements in site-specific cancer therapy and personalized oncomedicine. The development of nanomedicines explicitly targeted to cancer cells represents a pivotal breakthrough, allowing the development of precise interventions. These cancer-cell-targeted nanomedicines operate within the intricate milieu of the tumour microenvironment, further enhancing their therapeutic efficacy. This comprehensive review provides a contemporary perspective on precision cancer medicine and underscores the critical role of nanotechnology in advancing site-specific cancer therapy and personalized oncomedicine. It explores the categorization of nanoparticle types, distinguishing between organic and inorganic variants, and examines their significance in the targeted delivery of anticancer drugs. Current insights into the strategies for developing actively targeted nanomedicines across various cancer types are also provided, thus addressing relevant challenges associated with drug delivery barriers. Promising future directions in personalized cancer nanomedicine approaches are delivered, emphasising the imperative for continued optimization of nanocarriers in precision cancer medicine. The discussion underscores translational research's need to enhance cancer patients' outcomes by refining nanocarrier technologies in nanotechnology-driven, site-specific cancer therapy.
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Affiliation(s)
- Kamelia Hristova-Panusheva
- Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. Georgi Bonchev” Str., Bl. 21, 1113 Sofia, Bulgaria; (K.H.-P.); (C.X.)
| | - Charilaos Xenodochidis
- Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. Georgi Bonchev” Str., Bl. 21, 1113 Sofia, Bulgaria; (K.H.-P.); (C.X.)
| | - Milena Georgieva
- Institute of Molecular Biology “Acad. R. Tsanev”, Bulgarian Academy of Sciences, “Acad. Georgi Bonchev” Str., Bl. 21, 1113 Sofia, Bulgaria;
| | - Natalia Krasteva
- Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. Georgi Bonchev” Str., Bl. 21, 1113 Sofia, Bulgaria; (K.H.-P.); (C.X.)
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45
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Shen H, Zhang C, Li S, Liang Y, Lee LT, Aggarwal N, Wun KS, Liu J, Nadarajan SP, Weng C, Ling H, Tay JK, Wang DY, Yao SQ, Hwang IY, Lee YS, Chang MW. Prodrug-conjugated tumor-seeking commensals for targeted cancer therapy. Nat Commun 2024; 15:4343. [PMID: 38773197 PMCID: PMC11109227 DOI: 10.1038/s41467-024-48661-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 05/08/2024] [Indexed: 05/23/2024] Open
Abstract
Prodrugs have been explored as an alternative to conventional chemotherapy; however, their target specificity remains limited. The tumor microenvironment harbors a range of microorganisms that potentially serve as tumor-targeting vectors for delivering prodrugs. In this study, we harness bacteria-cancer interactions native to the tumor microbiome to achieve high target specificity for prodrug delivery. We identify an oral commensal strain of Lactobacillus plantarum with an intrinsic cancer-binding mechanism and engineer the strain to enable the surface loading of anticancer prodrugs, with nasopharyngeal carcinoma (NPC) as a model cancer. The engineered commensals show specific binding to NPC via OppA-mediated recognition of surface heparan sulfate, and the loaded prodrugs are activated by tumor-associated biosignals to release SN-38, a chemotherapy compound, near NPC. In vitro experiments demonstrate that the prodrug-loaded microbes significantly increase the potency of SN-38 against NPC cell lines, up to 10-fold. In a mouse xenograft model, intravenous injection of the engineered L. plantarum leads to bacterial colonization in NPC tumors and a 67% inhibition in tumor growth, enhancing the efficacy of SN-38 by 54%.
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Affiliation(s)
- Haosheng Shen
- NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore
- Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National Centre for Engineering Biology (NCEB), Singapore, Singapore
| | - Changyu Zhang
- Ningbo Institute of Dalian University of Technology, Ningbo, China
- Department of Chemistry, National University of Singapore, Singapore, Singapore
| | - Shengjie Li
- NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore
- Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Yuanmei Liang
- NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore
- Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National Centre for Engineering Biology (NCEB), Singapore, Singapore
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Li Ting Lee
- NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore
- Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National Centre for Engineering Biology (NCEB), Singapore, Singapore
| | - Nikhil Aggarwal
- NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore
- Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National Centre for Engineering Biology (NCEB), Singapore, Singapore
| | - Kwok Soon Wun
- NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore
- Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- National Centre for Engineering Biology (NCEB), Singapore, Singapore
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jing Liu
- Department of Otolaryngology, Infectious Diseases Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Saravanan Prabhu Nadarajan
- NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore
- Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Cheng Weng
- Department of Chemistry, National University of Singapore, Singapore, Singapore
| | - Hua Ling
- NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore
- Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Wilmar International Limited, Singapore, Singapore
| | - Joshua K Tay
- NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore
- Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Otolaryngology-Head and Neck Surgery, National University of Singapore, Singapore, Singapore
| | - De Yun Wang
- Department of Otolaryngology, Infectious Diseases Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Shao Q Yao
- Department of Chemistry, National University of Singapore, Singapore, Singapore
| | - In Young Hwang
- NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore.
- Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- Food, Chemical and Biotechnology, Singapore Institute of Technology, Singapore, Singapore.
| | - Yung Seng Lee
- NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore
- Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Matthew Wook Chang
- NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore.
- Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- National Centre for Engineering Biology (NCEB), Singapore, Singapore.
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
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Masoumi Godgaz S, Asefnejad A, Bahrami SH. Fabrication of PEGylated SPIONs-Loaded Niosome for Codelivery of Paclitaxel and Trastuzumab for Breast Cancer Treatment: In Vivo Study. ACS APPLIED BIO MATERIALS 2024; 7:2951-2965. [PMID: 38602218 DOI: 10.1021/acsabm.4c00027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/12/2024]
Abstract
There is a growing appeal for engineering drug delivery systems for controlled and local drug delivery. Conjugation of antibodies on the nanocarriers for targeted chemotherapeutic drugs has always been one of the main techniques. This work aims to develop a polycaprolactone/chitosan electrospun mat incorporated with paclitaxel/Fe3O4-loaded niosomes (SPNs) decorated with trastuzumab (TbNs) for cancer therapy. SPNs and TbNs were analyzed by DLS, zeta potential, scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. Fabricated mats with distinct concentrations of TbNs were classified into four groups (G0 (0), G1 (1), G2 (2.5), and G3 (5%)) and were studied physicochemically, mechanically, and biologically. Paclitaxel release was also studied for 7 days under an alternative magnetic field (AMF). The optimized mat was nominated for an in vivo study to evaluate its tumor growth inhibition. Based on the results, the TbNs had a spherical core and shell morphology with a smooth surface. The zeta potential and the mean size of TbNs were equal to -14.7 mV and 221 nm. TbNs did not affect the morphology and quality of nanofibers, but in general, the presence of TbNs increased the elastic modulus, water uptake, and degradation. Regarding the release study, AMF showed a significant increase in accelerating paclitaxel release from mats, and most releases belonged to the mat with 5% of TbNs. Results from the in vivo study showed the effective and synergistic effects of AMF on drug release and significant tumor growth inhibition. To summarize, the proposed nanocarrier under AMF can be a good candidate for cancer therapy.
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Affiliation(s)
- Saeideh Masoumi Godgaz
- Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran 1477893855,Iran
| | - Azadeh Asefnejad
- Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran 1477893855,Iran
| | - S Hajir Bahrami
- Department of Textile Engineering, Amirkabir University of Technology, Tehran15875-4413,Iran
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47
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Zenze M, Singh M. Receptor Targeting Using Copolymer-Modified Gold Nanoparticles for pCMV-Luc Gene Delivery to Liver Cancer Cells In Vitro. Int J Mol Sci 2024; 25:5016. [PMID: 38732235 PMCID: PMC11084699 DOI: 10.3390/ijms25095016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 04/30/2024] [Accepted: 05/02/2024] [Indexed: 05/13/2024] Open
Abstract
The formulation of novel delivery protocols for the targeted delivery of genes into hepatocytes by receptor mediation is important for the treatment of liver-specific disorders, including cancer. Non-viral delivery methods have been extensively studied for gene therapy. Gold nanoparticles (AuNPs) have gained attention in nanomedicine due to their biocompatibility. In this study, AuNPs were synthesized and coated with polymers: chitosan (CS), and polyethylene glycol (PEG). The targeting moiety, lactobionic acid (LA), was added for hepatocyte-specific delivery. Physicochemical characterization revealed that all nano-formulations were spherical and monodispersed, with hydrodynamic sizes between 70 and 250 nm. Nanocomplexes with pCMV-Luc DNA (pDNA) confirmed that the NPs could bind, compact, and protect the pDNA from nuclease degradation. Cytotoxicity studies revealed that the AuNPs were well tolerated (cell viabilities > 70%) in human hepatocellular carcinoma (HepG2), embryonic kidney (HEK293), and colorectal adenocarcinoma (Caco-2) cells, with enhanced transgene activity in all cells. The inclusion of LA in the NP formulation was notable in the HepG2 cells, which overexpress the asialoglycoprotein receptor on their cell surface. A five-fold increase in luciferase gene expression was evident for the LA-targeted AuNPs compared to the non-targeted AuNPs. These AuNPs have shown potential as safe and suitable targeted delivery vehicles for liver-directed gene therapy.
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Affiliation(s)
| | - Moganavelli Singh
- Nano-Gene and Drug Delivery Laboratory, Discipline of Biochemistry, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa;
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48
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Zimmer O, Goepferich A. On the uncertainty of the correlation between nanoparticle avidity and biodistribution. Eur J Pharm Biopharm 2024; 198:114240. [PMID: 38437906 DOI: 10.1016/j.ejpb.2024.114240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 02/05/2024] [Accepted: 02/28/2024] [Indexed: 03/06/2024]
Abstract
The specific delivery of a drug to its site of action also known as targeted drug delivery is a topic in the field of pharmaceutics studied for decades. One approach extensively investigated in this context is the use ligand functionalized nanoparticles. These particles are modified to carry receptor specific ligands, enabling them to accumulate at a desired target site. However, while this concept initially appears straightforward to implement, in-depth research has revealed several challenges hindering target site specific particle accumulation - some of which remain unresolved to this day. One of these challenges consists in the still incomplete understanding of how nanoparticles interact with biological systems. This knowledge gap significantly compromises the predictability of particle distribution in biological systems, which is critical for therapeutic efficacy. One of the most crucial steps in delivery is the attachment of nanoparticles to cells at the target site. This attachment occurs via the formation of multiple ligand receptor bonds. A process also referred to as multivalent interaction. While multivalency has been described extensively for individual molecules and macromolecules respectively, little is known on the multivalent binding of nanoparticles to cells. Here, we will specifically introduce the concept of avidity as a measure for favorable particle membrane interactions. Also, an overview about nanoparticle and membrane properties affecting avidity will be given. Thereafter, we provide a thorough review on literature investigating the correlation between nanoparticle avidity and success in targeted particle delivery. In particular, we want to analyze the currently uncertain data on the existence and nature of the correlation between particle avidity and biodistribution.
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Affiliation(s)
- Oliver Zimmer
- Department of Pharmaceutical Technology, University of Regensburg, Regensburg, Bavaria 93053, Germany
| | - Achim Goepferich
- Department of Pharmaceutical Technology, University of Regensburg, Regensburg, Bavaria 93053, Germany.
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49
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Wen Y, Li K, Ni M, Jiang H, Wu H, Yu Q, Li J, Li X, Wei J, Wu W, Xu H. Dendritic Polylysine with Paclitaxel and Triptolide Codelivery for Enhanced Cancer Ferroptosis through the Accumulation of ROS. ACS APPLIED MATERIALS & INTERFACES 2024. [PMID: 38597227 DOI: 10.1021/acsami.4c00558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/11/2024]
Abstract
Recently, paclitaxel (PTX) was reported to increase intracellular lipid reactive oxygen species (ROS) levels, triggering cancer cell ferroptosis. Based on this, some efforts had been made to improve PTX treatment for non-small-cell lung cancer (NSCLC). Our previous studies demonstrated that triptolide (TPL) could improve the antitumor effect of PTX. Nevertheless, the poor solubility and side effects often limit the application of chemotherapy drugs. In this paper, we constructed a novel nanodrug delivery system (NDDS) chemosynthesis by PEGylated generation 3 (G3) dendritic polylysine coloaded with PTX and TPL (PTX-TPL-PEG-PLL, PTPP), which was endowed with the ability of tumor targeting and favorable solubility. In addition, we demonstrated that TPL could induce ROS generation by regulating the NF-κB signaling pathway to enhance the ferroptosis-induced effect of PTX. Besides, ferroptosis induced by PTPP could improve chemoresistance through inhibiting the level of P-gp, GPX4, and SLC7A11. Furthermore, we determined that ferroptosis may strengthen the immune response by increasing the expression of CD8+ T cells and IFN-γ+ cells while decreasing Treg cells. In general, PTPP may be a potential system for NSCLC treatment.
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Affiliation(s)
- Yuanyuan Wen
- Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing 210009, China
| | - Kaiming Li
- Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Mengnan Ni
- Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Hui Jiang
- Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Haisi Wu
- Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Qinqi Yu
- Department of Geriatric Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210009, China
| | - Jinyu Li
- Department of Geriatric Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210009, China
| | - Xiaolin Li
- Department of Geriatric Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210009, China
| | - Jifu Wei
- Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing 210009, China
| | - Wei Wu
- School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China
| | - Huae Xu
- Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing 210009, China
- Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
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50
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Ma J, Li Y, Ying Y, Wu B, Liu Y, Zhou J, Hu L. Progress of Mesoporous Silica Coated Gold Nanorods for Biological Imaging and Cancer Therapy. ChemMedChem 2024; 19:e202300374. [PMID: 37990850 DOI: 10.1002/cmdc.202300374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 11/19/2023] [Accepted: 11/19/2023] [Indexed: 11/23/2023]
Abstract
For unique surface plasmon absorption and fluorescence characteristics, gold nanorods have been developed and widely employed in the biomedical field. However, limitations still exist due their low specific surface area, instability and tendency agglomerate in cytoplasm. Mesoporous silica materials have been broadly applied in field of catalysts, adsorbents, nanoreactors, and drug carriers due to its unique mesoporous structure, highly comparative surface area, good stability and biocompatibility. Therefore, coating gold nanorods with a dendritic mesopore channels can effectively prevent particle agglomeration, while increasing the specific surface area and drug loading efficiency. This review discusses the advancements of GNR@MSN in synthetic process, bio-imaging technique and tumor therapy. Additionally, the further application of GNR@MSN in imaging-guided treatment modalities is explored, while its promising superior application prospect is highlighted. Finally, the issues related to in vivo studies are critically examined for facilitating the transition of this promising nanoplatform into clinical trials.
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Affiliation(s)
- Jiaying Ma
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, University of South China, Hengyang, 421001, PR China
| | - Yongzhen Li
- Department of Pharmacy, School of Pharmacy, University of South China, Hengyang, 421001, PR China
| | - Yunfei Ying
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, University of South China, Hengyang, 421001, PR China
| | - Baibei Wu
- Department of Clinical Medicine, University of South China, Hengyang, 421001, PR China
| | - Yanmei Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, University of South China, Hengyang, 421001, PR China
| | - Juan Zhou
- School of Mechanical Engineering, University of South China, Hengyang, 421001, PR China
| | - Lidan Hu
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, University of South China, Hengyang, 421001, PR China
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