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Yadav PK, Chauhan D, Yadav P, Tiwari AK, Sultana N, Gupta D, Mishra K, Gayen JR, Wahajuddin M, Chourasia MK. Nanotechnology Assisted Drug Delivery Strategies for Chemotherapy: Recent Advances and Future Prospects. ACS APPLIED BIO MATERIALS 2025; 8:3601-3622. [PMID: 40318022 DOI: 10.1021/acsabm.5c00046] [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: 05/07/2025]
Abstract
In pursuit of the treatment of cancer, nanotechnology engineering has emerged as the simplest and most effective means, with the potential to deliver antitumor chemotherapeutics at the targeted site. Employing nanotechnology for drug delivery provides diverse nanosize particles ranging from one to a thousand nanometers. Reduced size improves drug bioavailability by increasing drug diffusion and decreasing the efflux rate. These nanocarriers offer an enormous scope for modification following the chemical and biological properties of both the drug and its disease. Moreover, these nanoformulations assist in targeting pharmaceutically active drug molecules to the desired site and have gained importance in recent years. Their modern use has revolutionized the antitumor action of many therapeutic agents. Higher drug loading efficiency, thermal stability, easy fabrication, low production cost, and large-scale industrial production draw attention to the application of nanotechnology as a better platform for the delivery of drug molecules. Furthermore, the interaction of nanocarrier technology-assisted agents lowers a drug's toxicity and therapeutic dosage, reduces drug tolerance, and enhances active drug concentration in neoplasm tissue, thus decreasing the concentration in healthy tissue. Nanotechnology-based medications are being widely explored and have depicted effective cancer management in vivo and in vitro systems, leading to many clinical trials with promising results. This review summarizes the innovative impact and application of different nanocarriers developed in recent years in cancer therapy. Subsequently, it also describes the essential findings and methodologies and their effects on cancer treatment. Compared with conventional therapy, nanomedicines can significantly improve the therapeutic effectiveness of antitumor drugs. Thus, the adverse effects associated with healthy tissues are decreased, and adverse effects are scaled back through enhanced permeability and retention effects. Lastly, future insights assisting nanotechnology in active therapeutics delivery and their scope in cancer chemotherapeutics have also been discussed.
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Affiliation(s)
- Pavan K Yadav
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Divya Chauhan
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Pooja Yadav
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Amrendra K Tiwari
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Nazneen Sultana
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
| | - Deepak Gupta
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
| | - Keerti Mishra
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
| | - Jiaur R Gayen
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
| | - Muhammad Wahajuddin
- Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Richmond Road, Bradford BD7 1DP, United Kingdom
| | - Manish K Chourasia
- Division of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
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Mahmoud YS, Hassanin IA, Sabra SA, Shehat MG, Abdel-Mohsen MA, Khattab SN, Hussein AA. Lipopolysaccharide nanomedicine-based reversion of chemotherapy-induced metastatic potential of breast cancer via hampering tumoral TLR4/SIRT2 axis and IL6 secretion from tumor-associated macrophages. Int J Biol Macromol 2025; 306:141396. [PMID: 39993692 DOI: 10.1016/j.ijbiomac.2025.141396] [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: 11/21/2024] [Revised: 02/17/2025] [Accepted: 02/20/2025] [Indexed: 02/26/2025]
Abstract
Triple-negative breast cancer (TNBC) is a metastatic disease. Targeted approaches, as implementing nanoliposomes, e.g., liposomal doxorubicin (DOX), did not exhibit significantly improved survival. Therefore, we aimed at reducing the metastatic potential of TNBC through a double punch to cancer cells and tumor-associated macrophages (TAMs). Databases' analyses showed that targeting TLR4/SIRT2 axis might be a possible option. Inspired by the emergence of lipopolysaccharide (LPS) in clinical trials, we developed bioactive copolymeric nanomicelles, originating from the self-assembly of our synthesized LPS-pectin conjugate (LPS-PEC) for the delivery of DOX (DOX@LPS-PEC). Targeting TLR4 via DOX@LPS-PEC micelles enhanced cellular uptake, however, it failed to significantly improve the cytotoxic potential of DOX. Alternatively, co-targeting SIRT2 via Sirtinol at a specific ratio (DOX@LPS-PEC: Sirtinol 1:5 w/w) elevated cellular oxidative stress, improved cytotoxic potential on 2D-monolayer and 3D-spheroid models, and significantly reduced migratory potential of MDA-MB-231 cells compared to DOX@LPS-PEC alone. Finally, DOX@LPS-PEC plus Sirtinol at the same ratio exhibited an ability to hamper TAM-secreted IL6, which contribute to the metastatic potential of TNBC. In conclusion, targeting TLR4/SIRT2 axis in TNBC synergizes with the effect of chemotherapeutics, e.g. DOX, reduce the metastatic potential of TNBC cells via down-regulating TLR4 and hampering tumor-microenvironment IL6.
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Affiliation(s)
- Yosra S Mahmoud
- Department of Biotechnology, Institute of Graduate Studies and Research (IGSR), Alexandria University, Alexandria, 21526, Egypt
| | - Islam A Hassanin
- Department of Biotechnology, Institute of Graduate Studies and Research (IGSR), Alexandria University, Alexandria, 21526, Egypt; Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
| | - Sally A Sabra
- Department of Biotechnology, Institute of Graduate Studies and Research (IGSR), Alexandria University, Alexandria, 21526, Egypt
| | - Michael G Shehat
- Department of Microbiology and Immunology, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
| | - Mohamed A Abdel-Mohsen
- Applied Medical Chemistry Department, Medical Research Institute, Alexandria University, Alexandria 21526, Egypt
| | - Sherine N Khattab
- Department of Chemistry, Faculty of Science, Alexandria University, Alexandria 21321, Egypt.
| | - Ahmed A Hussein
- Department of Biotechnology, Institute of Graduate Studies and Research (IGSR), Alexandria University, Alexandria, 21526, Egypt.
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Aalhate M, Mahajan S, Dhuri A, Singh PK. Biohybrid nano-platforms manifesting effective cancer therapy: Fabrication, characterization, challenges and clinical perspective. Adv Colloid Interface Sci 2025; 335:103331. [PMID: 39522420 DOI: 10.1016/j.cis.2024.103331] [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: 03/13/2024] [Revised: 10/01/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024]
Abstract
Nanotechnology-based delivery systems have brought a paradigm shift in the management of cancer. However, the main obstacles to nanocarrier-based delivery are their limited circulation duration, excessive immune clearance, inefficiency in interacting effectively in a biological context and overcoming biological barriers. This demands effective engineering of nanocarriers to achieve maximum efficacy. Nanocarriers can be maneuvered with biological components to acquire biological identity for further regulating their biodistribution and cell-to-cell cross-talk. Thus, the integration of synthetic and biological components to deliver therapeutic cargo is called a biohybrid delivery system. These delivery systems possess the advantage of synthetic nanocarriers, such as high drug loading, engineerable surface, reproducibility, adequate communication and immune evasion ability of biological constituents. The biohybrid delivery vectors offer an excellent opportunity to harness the synergistic properties of the best entities of the two worlds for improved therapeutic outputs. The major spotlights of this review are different biological components, synthetic counterparts of biohybrid nanocarriers, recent advances in hybridization techniques, and the design of biohybrid delivery systems for cancer therapy. Moreover, this review provides an overview of biohybrid systems with therapeutic and diagnostic applications. In a nutshell, this article summarizes the advantages and limitations of various biohybrid nano-platforms, their clinical potential and future directions for successful translation in cancer management.
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Affiliation(s)
- Mayur Aalhate
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, (NIPER), Hyderabad 500037, India
| | - Srushti Mahajan
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, (NIPER), Hyderabad 500037, India
| | - Anish Dhuri
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, (NIPER), Hyderabad 500037, India
| | - Pankaj Kumar Singh
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, (NIPER), Hyderabad 500037, India.
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Taeb S, Rostamzadeh D, Amini SM, Rahmati M, Golshekan M, Abedinzade M, Ahmadi E, Neha S, Najafi M. Revolutionizing Cancer Treatment: Harnessing the Power of Mesenchymal Stem Cells for Precise Targeted Therapy in the Tumor Microenvironment. Curr Top Med Chem 2025; 25:243-262. [PMID: 38797895 DOI: 10.2174/0115680266299112240514103048] [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: 12/17/2023] [Revised: 04/03/2024] [Accepted: 04/16/2024] [Indexed: 05/29/2024]
Abstract
In recent years, mesenchymal stem cells (MSCs) have emerged as promising anti-- cancer mediators with the potential to treat several cancers. MSCs have been modified to produce anti-proliferative, pro-apoptotic, and anti-angiogenic molecules that could be effective against a variety of malignancies. Additionally, customizing MSCs with cytokines that stimulate pro-tumorigenic immunity or using them as vehicles for traditional chemical molecules with anti-cancer characteristics. Even though the specific function of MSCs in tumors is still challenged, promising outcomes from preclinical investigations of MSC-based gene therapy for a variety of cancers inspire the beginning of clinical trials. In addition, the tumor microenvironment (TME) could have a substantial influence on normal tissue stem cells, which can affect the treatment outcomes. To overcome the complications of TME in cancer development, MSCs could provide some signs of hope for converting TME into unequivocal therapeutic tools. Hence, this review focuses on engineered MSCs (En-MSCs) as a promising approach to overcoming the complications of TME.
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Affiliation(s)
- Shahram Taeb
- Department of Radiology, School of Paramedical Sciences, Guilan University of Medical Sciences, Rasht, Iran
| | - Davoud Rostamzadeh
- Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, Connecticut, USA
| | - Seyed Mohammad Amini
- Radiation Biology Research center, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Rahmati
- Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Mostafa Golshekan
- Guilan Road Trauma Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Mahmoud Abedinzade
- Department of Medical Physiology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Elham Ahmadi
- Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, Connecticut, USA
| | - Singh Neha
- Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, Connecticut, USA
| | - Masoud Najafi
- Medical Technology Research Center, Institute of Health Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Bidooki SH, Quero J, Sánchez-Marco J, Herrero-Continente T, Marmol I, Lasheras R, Sebastian V, Arruebo M, Osada J, Rodriguez-Yoldi MJ. Squalene in Nanoparticles Improves Antiproliferative Effect on Human Colon Carcinoma Cells Through Apoptosis by Disturbances in Redox Balance. Int J Mol Sci 2024; 25:13048. [PMID: 39684759 DOI: 10.3390/ijms252313048] [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: 11/08/2024] [Revised: 11/25/2024] [Accepted: 12/02/2024] [Indexed: 12/18/2024] Open
Abstract
Squalene, a triterpene found in extra virgin olive oil, has therapeutic properties in diseases related to oxidative stress, such as cancer. However, its hydrophobic nature and susceptibility to oxidation limit its bioavailability outside of olive oil. To expand its applications, alternative delivery methods are necessary. The objective of the present study was to examine the impact of squalene encapsulated in PLGA (poly(lactic-co-glycolic) acid) nanoparticles (PLGA + Sq) on the proliferation of human colon carcinoma Caco-2 cells, as well as its underlying mechanism of action. The findings demonstrated that PLGA + Sq exert no influence on differentiated cells; however, it is capable of reducing the proliferation of undifferentiated Caco-2 cells through apoptosis and cell cycle arrest in the G1 phase. This effect was initiated by the release of cytochrome c into the cytoplasm and the subsequent activation of caspase-3. Furthermore, squalene exhibited pro-oxidant activity, as evidenced by an increase in intracellular ROS (reactive oxygen species) levels. The results of the squalene effect on genes associated with cell death, inflammation, and the cell cycle indicate that its antiproliferative effect may be post-transcriptional. In conclusion, PLGA + Sq demonstrate an antiproliferative effect on Caco-2 cells through apoptosis by altering redox balance, suggesting squalene's potential as a functional food ingredient for colorectal cancer prevention.
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Affiliation(s)
- Seyed Hesamoddin Bidooki
- Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, Spain
| | - Javier Quero
- Departamento de Farmacología, Fisiología, Medicina Legal y Forense, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, Spain
| | - Javier Sánchez-Marco
- Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, Spain
| | - Tania Herrero-Continente
- Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, Spain
| | - Inés Marmol
- Departamento de Farmacología, Fisiología, Medicina Legal y Forense, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, Spain
| | - Roberto Lasheras
- Laboratorio Agroambiental, Servicio de Seguridad Agroalimentaria de la Dirección General de Alimentación y Fomento Agroalimentario, Gobierno de Aragón, E-50071 Zaragoza, Spain
| | - Victor Sebastian
- Departamento de Ingeniería Química y Tecnologías del Medio Ambiente, Universidad de Zaragoza, E-50018 Zaragoza, Spain
- Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC, Universidad de Zaragoza, E-50009 Zaragoza, Spain
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain
| | - Manuel Arruebo
- Departamento de Ingeniería Química y Tecnologías del Medio Ambiente, Universidad de Zaragoza, E-50018 Zaragoza, Spain
- Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC, Universidad de Zaragoza, E-50009 Zaragoza, Spain
| | - Jesús Osada
- Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, Spain
- Instituto Agroalimentario de Aragón, CITA, Universidad de Zaragoza, E-50013 Zaragoza, Spain
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, E-28029 Madrid, Spain
| | - María Jesús Rodriguez-Yoldi
- Departamento de Farmacología, Fisiología, Medicina Legal y Forense, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, Spain
- Instituto Agroalimentario de Aragón, CITA, Universidad de Zaragoza, E-50013 Zaragoza, Spain
- CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, E-28029 Madrid, Spain
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Choudhury P, Kandula N, Kosuru R, Adena SKR. Nanomedicine: A great boon for cardiac regenerative medicine. Eur J Pharmacol 2024; 982:176969. [PMID: 39218342 DOI: 10.1016/j.ejphar.2024.176969] [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: 04/14/2024] [Revised: 08/28/2024] [Accepted: 08/29/2024] [Indexed: 09/04/2024]
Abstract
Cardiovascular disease (CVD) represents a significant global health challenge, remaining the leading cause of illness and mortality worldwide. The adult heart's limited regenerative capacity poses a major obstacle in repairing extensive damage caused by conditions like myocardial infarction. In response to these challenges, nanomedicine has emerged as a promising field aimed at improving treatment outcomes through innovative drug delivery strategies. Nanocarriers, such as nanoparticles (NPs), offer a revolutionary approach by facilitating targeted delivery of therapeutic agents directly to the heart. This precise delivery system holds immense potential for treating various cardiac conditions by addressing underlying mechanisms such as inflammation, oxidative stress, cell death, extracellular matrix remodeling, prosurvival signaling, and angiogenic pathways associated with ischemia-reperfusion injury. In this review, we provide a concise summary of the fundamental mechanisms involved in cardiac remodeling and regeneration. We explore how nanoparticle-based drug delivery systems can effectively target the afore-mentioned mechanisms. Furthermore, we discuss clinical trials that have utilized nanoparticle-based drug delivery systems specifically designed for cardiac applications. These trials demonstrate the potential of nanomedicine in clinical settings, paving the way for future advancements in cardiac therapeutics through precise and efficient drug delivery. Overall, nanomedicine holds promise in revolutionizing the treatment landscape of cardiovascular diseases by offering targeted and effective therapeutic strategies that address the complex pathophysiology of cardiac injuries.
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Affiliation(s)
- Priyanka Choudhury
- Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, 53226, USA
| | - Nirupama Kandula
- Department of Microbiology, GSL Medical College, Rajahmahendravaram, Andhra Pradesh, 533296, India
| | - Ramoji Kosuru
- Versiti Blood Research Institute, Milwaukee, WI, 53226, USA
| | - Sandeep Kumar Reddy Adena
- Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, 221005, India.
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Gonzalez-Melero L, Santos-Vizcaino E, Varela-Calvino R, Gomez-Tourino I, Asumendi A, Boyano MD, Igartua M, Hernandez RM. PLGA-PEI nanoparticle covered with poly(I:C) for personalised cancer immunotherapy. Drug Deliv Transl Res 2024; 14:2788-2803. [PMID: 38427275 PMCID: PMC11525302 DOI: 10.1007/s13346-024-01557-2] [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] [Accepted: 02/19/2024] [Indexed: 03/02/2024]
Abstract
Melanoma is the main cause of death among skin cancers and its incidence worldwide has been experiencing an appalling increase. However, traditional treatments lack effectiveness in advanced or metastatic patients. Immunotherapy, meanwhile, has been shown to be an effective treatment option, but the rate of cancers responding remains far from ideal. Here we have developed a personalized neoantigen peptide-based cancer vaccine by encapsulating patient derived melanoma neoantigens in polyethylenimine (PEI)-functionalised poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and coating them with polyinosinic:polycytidylic acid (poly(I:C)). We found that PLGA NPs can be effectively modified to be coated with the immunoadjuvant poly(I:C), as well as to encapsulate neoantigens. In addition, we found that both dendritic cells (DCs) and lymphocytes were effectively stimulated. Moreover, the developed NP was found to have a better immune activation profile than NP without poly(I:C) or without antigen. Our results demonstrate that the developed vaccine has a high capacity to activate the immune system, efficiently maturing DCs to present the antigen of choice and promoting the activity of lymphocytes to exert their cytotoxic function. Therefore, the immune response generated is optimal and specific for the elimination of melanoma tumour cells.
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Affiliation(s)
- Lorena Gonzalez-Melero
- NanoBioCel Research Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
- Bioaraba, NanoBioCel Research Group, Vitoria-Gasteiz, Spain
| | - Edorta Santos-Vizcaino
- NanoBioCel Research Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
- Bioaraba, NanoBioCel Research Group, Vitoria-Gasteiz, Spain
- Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Health Carlos III, Madrid, Spain
| | - Ruben Varela-Calvino
- Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Santiago de Compostela, Santiago, Spain
| | - Iria Gomez-Tourino
- Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela, Santiago, Spain
- Health Research Institute of Santiago de Compostela (IDIS), Santiago, Spain
| | - Aintzane Asumendi
- Biocruces Bizkaia Health Research Institute, 48903, Barakaldo, Spain
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940, Leioa, Spain
| | - Maria Dolores Boyano
- Biocruces Bizkaia Health Research Institute, 48903, Barakaldo, Spain
- Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940, Leioa, Spain
| | - Manoli Igartua
- NanoBioCel Research Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain.
- Bioaraba, NanoBioCel Research Group, Vitoria-Gasteiz, Spain.
- Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Health Carlos III, Madrid, Spain.
| | - Rosa Maria Hernandez
- NanoBioCel Research Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain.
- Bioaraba, NanoBioCel Research Group, Vitoria-Gasteiz, Spain.
- Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Health Carlos III, Madrid, Spain.
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Qi W, Yu Y, Yang C, Wang X, Jiang Y, Zhang L, Yu Z. Nanospheres as the delivery vehicle: novel application of Toxoplasma gondii ribosomal protein S2 in PLGA and chitosan nanospheres against acute toxoplasmosis. Front Immunol 2024; 15:1475280. [PMID: 39416787 PMCID: PMC11480959 DOI: 10.3389/fimmu.2024.1475280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Accepted: 09/09/2024] [Indexed: 10/19/2024] Open
Abstract
Toxoplasma gondii (T. gondii) is a zoonotic disease that poses great harm to humans and animals. So far, no effective T. gondii vaccine has been developed to provide fully protection against such parasites. Recently, numerous researches have focused on the use of poly-lactic-co-glycolic acid (PLGA) and chitosan (CS) for the vaccines against T. gondii infections. In this study, we employed PLGA and CS as the vehicles for T. gondii ribosome protein (TgRPS2) delivery. TgRPS2-PLGA and TgRPS2-CS nanospheres were synthesized by double emulsion solvent evaporation and ionic gelation technique as the nano vaccines. Before immunization in animals, the release efficacy and toxicity of the synthesized nanospheres were evaluated in vitro. Then, ICR mice were immunized intramuscularly, and immune protections of the synthesized nanospheres were assessed. The results showed that TgRPS2-PLGA and TgRPS2-CS nanospheres could induce higher levels of IgG and cytokines, activate dendritic cells, and promote the expression of histocompatibility complexes. The splenic lymphocyte proliferation and the enhancement in the proportion of CD4+ and CD8+ T lymphocytes were also observed in immunized animals. In addition, two types of nanospheres could significantly inhabit the replications of T. gondii in cardiac muscles and spleen tissues. All these obtained results in this study demonstrated that the TgRPS2 protein delivered by PLGA or CS nanospheres provided satisfactory immunoprotective effects in resisting T. gondii, and such formulations illustrated potential as prospective preventive agents for toxoplasmosis.
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Affiliation(s)
- WeiYu Qi
- College of animal science and technology, Ningxia University, Yinchuan, Ningxia, China
| | - YouLi Yu
- Institute of Animal Science, Ningxia Academy of Agricultural and Forestry Science, Yinchuan, China
| | - ChenChen Yang
- College of animal science and technology, Ningxia University, Yinchuan, Ningxia, China
| | - XiaoJuan Wang
- College of animal science and technology, Ningxia University, Yinchuan, Ningxia, China
| | - YuChen Jiang
- College of animal science and technology, Ningxia University, Yinchuan, Ningxia, China
| | - Li Zhang
- College of animal science and technology, Ningxia University, Yinchuan, Ningxia, China
| | - ZhengQing Yu
- College of animal science and technology, Ningxia University, Yinchuan, Ningxia, China
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Choudhury K, Sen P, Ghosh SS. SAHA potentiates the activity of repurposed drug promethazine loaded PLGA nanoparticles in triple-negative breast cancer cells. NANOTECHNOLOGY 2024; 35:465102. [PMID: 39146954 DOI: 10.1088/1361-6528/ad6fa6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 08/15/2024] [Indexed: 08/17/2024]
Abstract
Triple-negative breast cancer (TNBC) is considered the most aggressive form of breast cancer owing to the negative expression of targetable bioreceptors. Epithelial to mesenchymal transition (EMT) associated with metastatic abilities is its critical feature. As an attempt to target TNBC, nanotechnology was utilised to augment the effects of drug repurposing. Concerning that, a combination therapeutic module was structured with one of the aspects being a repurposed antihistamine, promethazine hydrochloride loaded PLGA nanoparticles. The as-synthesized nanoparticles were 217 nm in size and fluoresced at 522 nm, rendering them suitable for theranostic applications too. The second feature of the module was a common histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), used as a form of pre-treatment. Experimental studies demonstrated efficient cellular internalisation and significant innate anti-proliferative potential. The use of SAHA sensitised the cells to the drug loaded nanoparticle treatment. Mechanistic studies showed increase in ROS generation, mitochondrial dysfunction followed by apoptosis. Investigations into protein expression also revealed reduction of mesenchymal proteins like vimentin by 1.90 fold; while increase in epithelial marker like E-Cadherin by 1.42 fold, thus indicating an altered EMT dynamics. Further findings also provided better insight into the benefits of SAHA potentiated targeting of tumor spheroids that mimic solid tumors of TNBC. Thus, this study paves the avenue to a more rational translational validation of combining nanotherapeutics with drug repurposing.
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Affiliation(s)
- Konika Choudhury
- Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Plaboni Sen
- Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
| | - Siddhartha Sankar Ghosh
- Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
- Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
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10
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Wang J, Jiang W, Liu W, Xu T, Xu W, Sheng H, Badaila R, Ma M, Zhang N. Cytosolic delivery of cytochrome c conjugates induces apoptosis at nanomolar levels through a caspase-3-dependent pathway. Chem Commun (Camb) 2024; 60:8764-8767. [PMID: 39073564 DOI: 10.1039/d4cc02371d] [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: 07/30/2024]
Abstract
Cytochrome c (CytC) is conjugated with a small molecule TG6 to give TG6-CytC, which is directly delivered into cytosol, triggering the release of endogenous CytC from mitochondria, and inducing a caspase-3-dependent apoptosis with an IC50 down to 2.4 nM. This work shows an efficient strategy for intracellular protein delivery.
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Affiliation(s)
- Jian Wang
- School of Biology, Food, and Environment, Hefei University, Hefei, Anhui 230601, China.
| | - Wei Jiang
- School of Biology, Food, and Environment, Hefei University, Hefei, Anhui 230601, China.
| | - Wenjuan Liu
- School of Biology, Food, and Environment, Hefei University, Hefei, Anhui 230601, China.
| | - Tingting Xu
- School of Biology, Food, and Environment, Hefei University, Hefei, Anhui 230601, China.
| | - Wenqian Xu
- School of Biology, Food, and Environment, Hefei University, Hefei, Anhui 230601, China.
| | - Hongyang Sheng
- School of Biology, Food, and Environment, Hefei University, Hefei, Anhui 230601, China.
| | - Raman Badaila
- School of Biology, Food, and Environment, Hefei University, Hefei, Anhui 230601, China.
| | - Mingming Ma
- Key Laboratory of Precision and Intelligent Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China.
| | - Ning Zhang
- School of Biology, Food, and Environment, Hefei University, Hefei, Anhui 230601, China.
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11
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Bārzdiņa A, Plotniece A, Sobolev A, Pajuste K, Bandere D, Brangule A. From Polymeric Nanoformulations to Polyphenols-Strategies for Enhancing the Efficacy and Drug Delivery of Gentamicin. Antibiotics (Basel) 2024; 13:305. [PMID: 38666981 PMCID: PMC11047640 DOI: 10.3390/antibiotics13040305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 03/25/2024] [Accepted: 03/27/2024] [Indexed: 04/29/2024] Open
Abstract
Gentamicin is an essential broad-spectrum aminoglycoside antibiotic that is used in over 40 clinical conditions and has shown activity against a wide range of nosocomial, biofilm-forming, multi-drug resistant bacteria. Nevertheless, the low cellular penetration and serious side effects of gentamicin, as well as the fear of the development of antibacterial resistance, has led to a search for ways to circumvent these obstacles. This review provides an overview of the chemical and pharmacological properties of gentamicin and offers six different strategies (the isolation of specific types of gentamicin, encapsulation in polymeric nanoparticles, hydrophobization of the gentamicin molecule, and combinations of gentamicin with other antibiotics, polyphenols, and natural products) that aim to enhance the drug delivery and antibacterial activity of gentamicin. In addition, factors influencing the synthesis of gentamicin-loaded polymeric (poly (lactic-co-glycolic acid) (PLGA) and chitosan) nanoparticles and the methods used in drug release studies are discussed. Potential research directions and future perspectives for gentamicin-loaded drug delivery systems are given.
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Affiliation(s)
- Ance Bārzdiņa
- Department of Pharmaceutical Chemistry, Riga Stradins University, 21 Konsula Str., LV-1007 Riga, Latvia; (A.P.)
- Baltic Biomaterials Centre of Excellence, Headquarters at Riga Technical University, LV-1007 Riga, Latvia
| | - Aiva Plotniece
- Department of Pharmaceutical Chemistry, Riga Stradins University, 21 Konsula Str., LV-1007 Riga, Latvia; (A.P.)
- Latvian Institute of Organic Synthesis, 21 Aizkraukles Str., LV-1006 Riga, Latvia; (A.S.); (K.P.)
| | - Arkadij Sobolev
- Latvian Institute of Organic Synthesis, 21 Aizkraukles Str., LV-1006 Riga, Latvia; (A.S.); (K.P.)
| | - Karlis Pajuste
- Latvian Institute of Organic Synthesis, 21 Aizkraukles Str., LV-1006 Riga, Latvia; (A.S.); (K.P.)
| | - Dace Bandere
- Department of Pharmaceutical Chemistry, Riga Stradins University, 21 Konsula Str., LV-1007 Riga, Latvia; (A.P.)
- Baltic Biomaterials Centre of Excellence, Headquarters at Riga Technical University, LV-1007 Riga, Latvia
| | - Agnese Brangule
- Department of Pharmaceutical Chemistry, Riga Stradins University, 21 Konsula Str., LV-1007 Riga, Latvia; (A.P.)
- Baltic Biomaterials Centre of Excellence, Headquarters at Riga Technical University, LV-1007 Riga, Latvia
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12
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Bai S, Zhang XD, Zou YQ, Lin YX, Liu ZY, Li KW, Huang P, Yoshida T, Liu YL, Li MS, Zhang W, Wang XJ, Zhang M, Du C. Development of high-efficiency superparamagnetic drug delivery system with MPI imaging capability. Front Bioeng Biotechnol 2024; 12:1382085. [PMID: 38572358 PMCID: PMC10987818 DOI: 10.3389/fbioe.2024.1382085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 03/11/2024] [Indexed: 04/05/2024] Open
Abstract
In this study, a high-efficiency superparamagnetic drug delivery system was developed for preclinical treatment of bladder cancer in small animals. Two types of nanoparticles with magnetic particle imaging (MPI) capability, i.e., single- and multi-core superparamagnetic iron oxide nanoparticles (SPIONs), were selected and coupled with bladder anti-tumor drugs by a covalent coupling scheme. Owing to the minimal particle size, magnetic field strengths of 270 mT with a gradient of 3.2 T/m and 260 mT with a gradient of 3.7 T/m were found to be necessary to reach an average velocity of 2 mm/s for single- and multi-core SPIONs, respectively. To achieve this, a method of constructing an in vitro magnetic field for drug delivery was developed based on hollow multi-coils arranged coaxially in close rows, and magnetic field simulation was used to study the laws of the influence of the coil structure and parameters on the magnetic field. Using this method, a magnetic drug delivery system of single-core SPIONs was developed for rabbit bladder therapy. The delivery system consisted of three coaxially and equidistantly arranged coils with an inner diameter of Φ50 mm, radial height of 85 mm, and width of 15 mm that were positioned in close proximity to each other. CCK8 experimental results showed that the three types of drug-coupled SPION killed tumor cells effectively. By adjusting the axial and radial positions of the rabbit bladder within the inner hole of the delivery coil structure, the magnetic drugs injected could undergo two-dimensional delivery motions and were delivered and aggregated to the specified target location within 12 s, with an aggregation range of about 5 mm × 5 mm. In addition, the SPION distribution before and after delivery was imaged using a home-made open-bore MPI system that could realistically reflect the physical state. This study contributes to the development of local, rapid, and precise drug delivery and the visualization of this process during cancer therapy, and further research on MPI/delivery synchronization technology is planned for the future.
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Affiliation(s)
- Shi Bai
- Department of Information Engineering, Shenyang University of Technology, Shenyang, China
| | - Xiao-dan Zhang
- Department of Information Engineering, Shenyang University of Technology, Shenyang, China
| | - Yu-qi Zou
- Department of Information Engineering, Shenyang University of Technology, Shenyang, China
| | - Yu-xi Lin
- Department of Information Engineering, Shenyang University of Technology, Shenyang, China
| | - Zhi-yao Liu
- Department of Information Engineering, Shenyang University of Technology, Shenyang, China
| | - Ke-wen Li
- Department of Information Engineering, Shenyang University of Technology, Shenyang, China
| | - Ping Huang
- Department of Information Engineering, Shenyang University of Technology, Shenyang, China
| | - Takashi Yoshida
- Department of Electrical Engineering, Kyushu University, Fukuoka, Japan
| | - Yi-li Liu
- Department of Urology, Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Ming-shan Li
- Department of Urology, Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Wei Zhang
- Department of Oncology, General Hospital of Northern Theater Command, Shenyang, China
| | - Xiao-ju Wang
- Department of Foreign Languages, Liaoning Vocational and Technical College of Economics, Shenyang, China
| | - Min Zhang
- First Affiliated Hospital, China Medical University, Shenyang, China
| | - Cheng Du
- Department of Oncology, General Hospital of Northern Theater Command, Shenyang, China
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13
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Shin HJ, Kim IS, Choi SG, Lee K, Park H, Shin J, Kim D, Beom J, Yi YY, Gupta DP, Song GJ, Chung WS, Lee CJ, Kim DW. Rejuvenating aged microglia by p16 ink4a-siRNA-loaded nanoparticles increases amyloid-β clearance in animal models of Alzheimer's disease. Mol Neurodegener 2024; 19:25. [PMID: 38493185 PMCID: PMC10943801 DOI: 10.1186/s13024-024-00715-x] [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: 09/25/2023] [Accepted: 02/27/2024] [Indexed: 03/18/2024] Open
Abstract
Age-dependent accumulation of amyloid plaques in patients with sporadic Alzheimer's disease (AD) is associated with reduced amyloid clearance. Older microglia have a reduced ability to phagocytose amyloid, so phagocytosis of amyloid plaques by microglia could be regulated to prevent amyloid accumulation. Furthermore, considering the aging-related disruption of cell cycle machinery in old microglia, we hypothesize that regulating their cell cycle could rejuvenate them and enhance their ability to promote more efficient amyloid clearance. First, we used gene ontology analysis of microglia from young and old mice to identify differential expression of cyclin-dependent kinase inhibitor 2A (p16ink4a), a cell cycle factor related to aging. We found that p16ink4a expression was increased in microglia near amyloid plaques in brain tissue from patients with AD and 5XFAD mice, a model of AD. In BV2 microglia, small interfering RNA (siRNA)-mediated p16ink4a downregulation transformed microglia with enhanced amyloid phagocytic capacity through regulated the cell cycle and increased cell proliferation. To regulate microglial phagocytosis by gene transduction, we used poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles, which predominantly target microglia, to deliver the siRNA and to control microglial reactivity. Nanoparticle-based delivery of p16ink4a siRNA reduced amyloid plaque formation and the number of aged microglia surrounding the plaque and reversed learning deterioration and spatial memory deficits. We propose that downregulation of p16ink4a in microglia is a promising strategy for the treatment of Alzheimer's disease.
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Affiliation(s)
- Hyo Jung Shin
- Department of Anatomy and Cell Biology, Chungnam National University College of Medicine, Daejeon, Republic of Korea
- Brain Research Institute, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - In Soo Kim
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea
- Department of Pharmacology, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Seung Gyu Choi
- Department of Anatomy and Cell Biology, Chungnam National University College of Medicine, Daejeon, Republic of Korea
- Brain Research Institute, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Kayoung Lee
- Department of Anatomy and Cell Biology, Chungnam National University College of Medicine, Daejeon, Republic of Korea
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea
- Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Hyewon Park
- Department of Anatomy and Cell Biology, Chungnam National University College of Medicine, Daejeon, Republic of Korea
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Juhee Shin
- Department of Anatomy and Cell Biology, Chungnam National University College of Medicine, Daejeon, Republic of Korea
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Dayoung Kim
- Department of Anatomy and Cell Biology, Chungnam National University College of Medicine, Daejeon, Republic of Korea
| | - Jaewon Beom
- Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Yoon Young Yi
- Department of Pediatrics, College of Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea
| | - Deepak Prasad Gupta
- Department of Medicine, College of Medicine, Catholic Kwandong University, Gangneung, Gangwon-Do, Republic of Korea
| | - Gyun Jee Song
- Department of Medicine, College of Medicine, Catholic Kwandong University, Gangneung, Gangwon-Do, Republic of Korea
- Translational Brain Research Center, International St. Mary's Hospital, Catholic Kwandong University, Incheon, Republic of Korea
| | - Won-Suk Chung
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea
| | - C Justin Lee
- Center for Glia-Neuron Interaction, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea
- Center for Cognition and Sociality, Institute for Basic Science, Daejeon, Republic of Korea
| | - Dong Woon Kim
- Department of Anatomy and Cell Biology, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
- Brain Research Institute, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
- Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea.
- Department of Oral Anatomy and Developmental Biology, College of Dentistry Kyung Hee University, Seoul, Republic of Korea.
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14
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Scully MA, Wilhelm R, Wilkins DE, Day ES. Membrane-Cloaked Nanoparticles for RNA Interference of β-Catenin in Triple-Negative Breast Cancer. ACS Biomater Sci Eng 2024; 10:1355-1363. [PMID: 38306303 PMCID: PMC10939768 DOI: 10.1021/acsbiomaterials.4c00160] [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] [Indexed: 02/04/2024]
Abstract
There is an outstanding need for targeted therapies for triple-negative breast cancer (TNBC), an aggressive breast cancer subtype. Since TNBC's rapid growth and metastasis are driven by hyperactive Wnt signaling, suppressing the key-pathway mediator β-catenin through RNA interference may improve patient outcomes. However, small interfering ribonucleic acid (siRNA) molecules require a carrier to elicit targeted gene silencing. Here, we show that 4T1 cancer cell membrane wrapped poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) can deliver siRNA into TNBC cells, silence β-catenin expression, and reduce the cells' tumorigenic qualities. Compared to unwrapped and nontargeted NPs, the cancer cell membrane wrapped nanoparticles (CCNPs) exhibit dramatically improved uptake by TNBC cells versus breast epithelial cells and greater gene silencing at mRNA and protein levels. Congruently, β-catenin siRNA-loaded CCNPs significantly activate senescence in 2D cultured TNBC cells and reduce proliferation in 3D spheroids. This work advances the development of nucleic acid carriers for targeted RNA interference therapy.
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Affiliation(s)
- Mackenzie A Scully
- Department of Biomedical Engineering, University of Delaware, Newark, Delaware 19713, United States of America
| | - Ruth Wilhelm
- Department of Biomedical Engineering, University of Delaware, Newark, Delaware 19713, United States of America
| | - Dana E Wilkins
- Department of Biomedical Engineering, University of Delaware, Newark, Delaware 19713, United States of America
| | - Emily S Day
- Department of Biomedical Engineering, University of Delaware, Newark, Delaware 19713, United States of America
- Department of Materials Science and Engineering, University of Delaware, Newark, Delaware 19716, United States of America
- Center for Translational Research, Helen F. Graham Cancer Center and Research Institute, Newark, Delaware 19713, United States of America
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15
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Cooper CG, Kafetzis KN, Patabendige A, Tagalakis AD. Blood-brain barrier disruption in dementia: Nano-solutions as new treatment options. Eur J Neurosci 2024; 59:1359-1385. [PMID: 38154805 DOI: 10.1111/ejn.16229] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 11/28/2023] [Accepted: 12/02/2023] [Indexed: 12/30/2023]
Abstract
Candidate drugs targeting the central nervous system (CNS) demonstrate extremely low clinical success rates, with more than 98% of potential treatments being discontinued due to poor blood-brain barrier (BBB) permeability. Neurological conditions were shown to be the second leading cause of death globally in 2016, with the number of people currently affected by neurological disorders increasing rapidly. This increasing trend, along with an inability to develop BBB permeating drugs, is presenting a major hurdle in the treatment of CNS-related disorders, like dementia. To overcome this, it is necessary to understand the structure and function of the BBB, including the transport of molecules across its interface in both healthy and pathological conditions. The use of CNS drug carriers is rapidly gaining popularity in CNS research due to their ability to target BBB transport systems. Further research and development of drug delivery vehicles could provide essential information that can be used to develop novel treatments for neurological conditions. This review discusses the BBB and its transport systems and evaluates the potential of using nanoparticle-based delivery systems as drug carriers for CNS disease with a focus on dementia.
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Affiliation(s)
| | | | - Adjanie Patabendige
- Department of Biology, Edge Hill University, Ormskirk, UK
- Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, UK
| | - Aristides D Tagalakis
- Department of Biology, Edge Hill University, Ormskirk, UK
- UCL Great Ormond Street Institute of Child Health, University College London, London, UK
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16
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Neetika, Sharma M, Thakur P, Gaur P, Rani GM, Rustagi S, Talreja RK, Chaudhary V. Cancer treatment and toxicity outlook of nanoparticles. ENVIRONMENTAL RESEARCH 2023; 237:116870. [PMID: 37567383 DOI: 10.1016/j.envres.2023.116870] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 08/02/2023] [Accepted: 08/09/2023] [Indexed: 08/13/2023]
Abstract
Diversified nanosystems with tunable physicochemical attributes have emerged as potential solution to globally devastating cancer by offering novel possibilities for improving the techniques of cancer detection, imaging, therapies, diagnosis, drug delivery and treatment. Drug delivery systems based on nanoparticles (NPs) with ability of crossing different biological barriers are becoming increasingly popular. Besides, NPs are utilized in pharmaceutical sciences to mitigate the toxicity of conventional cancer therapeutics. However, significant NPs-associated toxicity, off-targeted activities, and low biocompatibility limit their utilization for cancer theranostics and can be hazardous to cancer patients up to life-threatening conditions. NPs interact with the biomolecules and disturb their regular function by aggregating inside cells and forming a protein corona, and the formulation turns ineffective in controlling cancer cell growth. The adverse interactions between NPs and biological entities can lead to life-threatening toxicities. This review focuses on the widespread use of various NPs including zinc oxide, titanium oxide, silver, and gold, which serve as efficient nano-vehicles and demonstrate notable pharmacokinetic and pharmacodynamic advantages in cancer therapy. Subsequently, the mechanism of nanotoxicity attached with these NPs, alternate solutions and their prospect to revolutionize cancer theranostics are highlighted. This review will serve as guide for future developments associated with high-performance NPs with controlled toxicity for establishing them as modern-age nanotools to manage cancer in tailored manner.
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Affiliation(s)
- Neetika
- School of Biological and Environmental Sciences, Shoolini University, Solan, 173212, India
| | - Mamta Sharma
- School of Biological and Environmental Sciences, Shoolini University, Solan, 173212, India.
| | - Pankaj Thakur
- Special Centre for Nanoscience, Jawaharlal Nehru University, New Delhi, 110067, India
| | - Paras Gaur
- Department of Biochemistry and Molecular Biology, Carver College of Medicine, University of Iowa, Iowa, 52242, United States
| | - Gokana Mohana Rani
- Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Keelung Road, Taipei, 10607, Taiwan, ROC.
| | - Sarvesh Rustagi
- School of Applied and Life Sciences, Uttranchal University, Dehradun, Uttrakhand, India
| | - Rishi Kumar Talreja
- Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, 110029, India
| | - Vishal Chaudhary
- Physics Department, Bhagini Nivedita College, University of Delhi, Delhi, India.
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17
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Zhu W, Li W, Yao M, Wang Y, Zhang W, Li C, Wang X, Chen W, Lv H. Mineralized Collagen/Polylactic Acid Composite Scaffolds for Load-Bearing Bone Regeneration in a Developmental Model. Polymers (Basel) 2023; 15:4194. [PMID: 37896438 PMCID: PMC10610794 DOI: 10.3390/polym15204194] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Revised: 09/23/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
Repairing load-bearing bone defects in children remains a big clinical challenge. Mineralized collagen (MC) can effectively simulate natural bone composition and hierarchical structure and has a good biocompatibility and bone conductivity. Polylactic acid (PLA) is regarded as a gold material because of its mechanical properties and degradability. In this study, we prepare MC/PLA composite scaffolds via in situ mineralization and freeze-drying. Cell, characterization, and animal experiments compare and evaluate the biomimetic properties and repair effects of the MC/PLA scaffolds. Phalloidin and DAPI staining results show that the MC/PLA scaffolds are not cytotoxic. CCK-8 and scratch experiments prove that the scaffolds are superior to MC and hydroxyapatite (HA)/PLA scaffolds in promoting cell proliferation and migration. The surface and interior of the MC/PLA scaffolds exhibit rich interconnected pore structures with a porosity of ≥70%. The XRD patterns are typical HA waveforms. X-ray, micro-CT, and H&E staining reveal that the defect boundary disappears, new bone tissue grows into MC/PLA scaffolds in a large area, and the scaffolds are degraded after six months of implantation. The MC/PLA composite scaffold has a pore structure and composition similar to cancellous bone, with a good biocompatibility and bone regeneration ability.
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Affiliation(s)
- Wenbo Zhu
- Department of Orthopaedic Surgery, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Shijiazhuang 050051, China; (W.Z.); (W.L.); (M.Y.); (Y.W.); (C.L.)
- Key Laboratory of Biomechanics of Hebei Province, Orthopaedic Research Institution of Hebei Province, No. 139 Ziqiang Road, Shijiazhuang 050051, China
- National Health Commission Key Laboratory of Intelligent Orthopaedic Equipment, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Shijiazhuang 050051, China
| | - Wenjing Li
- Department of Orthopaedic Surgery, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Shijiazhuang 050051, China; (W.Z.); (W.L.); (M.Y.); (Y.W.); (C.L.)
- Key Laboratory of Biomechanics of Hebei Province, Orthopaedic Research Institution of Hebei Province, No. 139 Ziqiang Road, Shijiazhuang 050051, China
- National Health Commission Key Laboratory of Intelligent Orthopaedic Equipment, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Shijiazhuang 050051, China
| | - Mengxuan Yao
- Department of Orthopaedic Surgery, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Shijiazhuang 050051, China; (W.Z.); (W.L.); (M.Y.); (Y.W.); (C.L.)
- Key Laboratory of Biomechanics of Hebei Province, Orthopaedic Research Institution of Hebei Province, No. 139 Ziqiang Road, Shijiazhuang 050051, China
- National Health Commission Key Laboratory of Intelligent Orthopaedic Equipment, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Shijiazhuang 050051, China
| | - Yan Wang
- Department of Orthopaedic Surgery, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Shijiazhuang 050051, China; (W.Z.); (W.L.); (M.Y.); (Y.W.); (C.L.)
- Key Laboratory of Biomechanics of Hebei Province, Orthopaedic Research Institution of Hebei Province, No. 139 Ziqiang Road, Shijiazhuang 050051, China
- National Health Commission Key Laboratory of Intelligent Orthopaedic Equipment, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Shijiazhuang 050051, China
| | - Wei Zhang
- Department of Pathology, Hebei Medical University, No. 361 Zhongshan Road, Shijiazhuang 050017, China;
| | - Chao Li
- Department of Orthopaedic Surgery, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Shijiazhuang 050051, China; (W.Z.); (W.L.); (M.Y.); (Y.W.); (C.L.)
- Key Laboratory of Biomechanics of Hebei Province, Orthopaedic Research Institution of Hebei Province, No. 139 Ziqiang Road, Shijiazhuang 050051, China
- National Health Commission Key Laboratory of Intelligent Orthopaedic Equipment, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Shijiazhuang 050051, China
| | - Xiumei Wang
- State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, No. 30 Shuangqing Road, Beijing 100084, China;
| | - Wei Chen
- Department of Orthopaedic Surgery, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Shijiazhuang 050051, China; (W.Z.); (W.L.); (M.Y.); (Y.W.); (C.L.)
- Key Laboratory of Biomechanics of Hebei Province, Orthopaedic Research Institution of Hebei Province, No. 139 Ziqiang Road, Shijiazhuang 050051, China
- National Health Commission Key Laboratory of Intelligent Orthopaedic Equipment, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Shijiazhuang 050051, China
| | - Hongzhi Lv
- Department of Orthopaedic Surgery, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Shijiazhuang 050051, China; (W.Z.); (W.L.); (M.Y.); (Y.W.); (C.L.)
- Key Laboratory of Biomechanics of Hebei Province, Orthopaedic Research Institution of Hebei Province, No. 139 Ziqiang Road, Shijiazhuang 050051, China
- National Health Commission Key Laboratory of Intelligent Orthopaedic Equipment, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Shijiazhuang 050051, China
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18
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Sonam Dongsar T, Tsering Dongsar T, Molugulu N, Annadurai S, Wahab S, Gupta N, Kesharwani P. Targeted therapy of breast tumor by PLGA-based nanostructures: The versatile function in doxorubicin delivery. ENVIRONMENTAL RESEARCH 2023; 233:116455. [PMID: 37356522 DOI: 10.1016/j.envres.2023.116455] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 06/15/2023] [Accepted: 06/17/2023] [Indexed: 06/27/2023]
Abstract
Breast carcinoma is a molecularly diverse illness, and it is among the most prominent and often reported malignancies in female across the globe. Surgical intervention, chemotherapy, immunotherapy, gene therapy, and endocrine treatment are among the currently viable treatment options for the carcinoma of breast. Chemotherapy is among the most prevalent cancer management strategy. Doxorubicin (DOX) widely employed as a cytostatic medication for the treatment of a variety of malignancies. Despite its widespread acceptance and excellent efficacy against an extensive line up of neoplasia, it has a variety of shortcomings that limit its therapeutic potential in the previously mentioned indications. Employment of nanoparticulate systems has come up as a unique chemo medication delivery strategy and are being considerably explored for the amelioration of breast carcinoma. Polylactic-co-glycolic acid (PLGA)-based nano systems are being utilized in a number of areas within the medical research and medication delivery constitutes one of the primary functions for PLGA given their inherent physiochemical attributes, including their aqueous solubility, biocompatibility, biodegradability, versatility in formulation, and limited toxicity. Herein along with the different application of PLGA-based nano formulations in cancer therapy, the present review intends to describe the various research investigations that have been conducted to enumerate the effectiveness of DOX-encapsulated PLGA nanoparticles (DOX-PLGA NPs) as a feasible treatment option for breast cancer.
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Affiliation(s)
- Tenzin Sonam Dongsar
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India
| | - Tenzin Tsering Dongsar
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India
| | - Nagashekhara Molugulu
- School of Pharmacy, Monash University, Bandar Sunway, Jalan Lagoon Selatan, 47500, Malaysia
| | - Sivakumar Annadurai
- Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia
| | - Shadma Wahab
- Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia
| | - Neelima Gupta
- Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, Madhya Pradesh, 470003, India
| | - Prashant Kesharwani
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India; Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
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19
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Almomen A, Badran M, Alhowyan AA, Alkholief M, Alshamsan A. Imiquimod-Loaded Chitosan-Decorated Di-Block and Tri-Block Polymeric Nanoparticles Loaded In Situ Gel for the Management of Cervical Cancer. Gels 2023; 9:713. [PMID: 37754394 PMCID: PMC10530705 DOI: 10.3390/gels9090713] [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: 07/25/2023] [Revised: 08/20/2023] [Accepted: 08/28/2023] [Indexed: 09/28/2023] Open
Abstract
BACKGROUND Cervical intraepithelial neoplasia, the predisposing factor for cervical cancer (CC), is caused by human papillomavirus (HPV) infection and can be treated with imiquimod (IMQ). However, poor water solubility and side effects such as local inflammation can render IMQ ineffective. The aim of this study is to design a prolonged release nano system in combination with mucoadhesive-thermosensitive properties for an effective vaginal drug delivery. METHODS Polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL), poly lactide-co-caprolactone (PLA-PCL), and poly L-lactide-co-caprolactone-co-glycolide (PLGA-PCL) were used to create IMQ nanoparticles. Chitosan (CS) was then added to the surfaces of the IMQ NPs for its mucoadhesive properties. The NPs were then incorporated into poloxamer hydrogels. The NPs' size and morphology, encapsulation efficiency (EE), in vitro drug release, gel characterization, ex vivo drug permeation, and in vitro safety and efficacy were characterized. RESULTS Two batches of NPs were prepared, IMQ NPs and CS-coated NPs (CS-IMQ NPs). In general, both types of NPs were uniformly spherical in shape with average particle sizes of 237.3 ± 4.7 and 278.2 ± 5.4 nm and EE% of 61.48 ± 5.19% and 37.73 ± 2.88 for IMQ NPs and CS-IMQ NPs, respectively. Both systems showed prolonged drug release of about 80 and 70% for IMQ NPs and CS-IMQ NPs, respectively, within 48 h. The gelation temperatures for the IMQ NPs and CS-IMQ NPs were 30 and 32 °C, respectively; thus, suitable for vaginal application. Although ex vivo permeability showed that CS-IMQ NPs showed superior penetration compared to IMQ NPs, both systems enhanced drug penetration (283 and 462 µg/cm2 for IMQ NPs and CS-IMQ NPs, respectively) relative to the control (60 µg/cm2). Both systems reduced the viability of cervical cancer cells, with a minimal effect of the normal vaginal epithelium. However, IMQ NPs exhibited a more pronounced cytotoxic effect. Both systems were able to reduce the production of inflammatory cytokines by at least 25% in comparison to free IMQ. CONCLUSION IMQ and CS-IMQ NP in situ gels enhanced stability and drug release, and improved IMQ penetration through the vaginal tissues. Additionally, the new systems were able to increase the cytotoxic effect of IMQ against CC cells with a reduction in inflammatory responses. Thus, we believe that these systems could be a good alternative to commercial IMQ systems for the management of CC.
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Affiliation(s)
- Aliyah Almomen
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia
| | - Mohamed Badran
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia; (M.B.); (A.A.A.); (M.A.); (A.A.)
| | - Adel Ali Alhowyan
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia; (M.B.); (A.A.A.); (M.A.); (A.A.)
| | - Musaed Alkholief
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia; (M.B.); (A.A.A.); (M.A.); (A.A.)
| | - Aws Alshamsan
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia; (M.B.); (A.A.A.); (M.A.); (A.A.)
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20
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Shakya AK, Al-Sulaibi M, Naik RR, Nsairat H, Suboh S, Abulaila A. Review on PLGA Polymer Based Nanoparticles with Antimicrobial Properties and Their Application in Various Medical Conditions or Infections. Polymers (Basel) 2023; 15:3597. [PMID: 37688223 PMCID: PMC10490122 DOI: 10.3390/polym15173597] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/19/2023] [Accepted: 08/25/2023] [Indexed: 09/10/2023] Open
Abstract
The rise in the resistance to antibiotics is due to their inappropriate use and the use of a broad spectrum of antibiotics. This has also contributed to the development of multidrug-resistant microorganisms, and due to the unavailability of suitable new drugs for treatments, it is difficult to control. Hence, there is a need for the development of new novel, target-specific antimicrobials. Nanotechnology, involving the synthesis of nanoparticles, may be one of the best options, as it can be manipulated by using physicochemical properties to develop intelligent NPs with desired properties. NPs, because of their unique properties, can deliver drugs to specific targets and release them in a sustained fashion. The chance of developing resistance is very low. Polymeric nanoparticles are solid colloids synthesized using either natural or synthetic polymers. These polymers are used as carriers of drugs to deliver them to the targets. NPs, synthesized using poly-lactic acid (PLA) or the copolymer of lactic and glycolic acid (PLGA), are used in the delivery of controlled drug release, as they are biodegradable, biocompatible and have been approved by the USFDA. In this article, we will be reviewing the synthesis of PLGA-based nanoparticles encapsulated or loaded with antibiotics, natural products, or metal ions and their antibacterial potential in various medical applications.
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Affiliation(s)
- Ashok K Shakya
- Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan
- Pharmacological and Diagnostic Research Center, Faculty of Pharmacy and Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan
| | - Mazen Al-Sulaibi
- Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan
- Pharmacological and Diagnostic Research Center, Faculty of Pharmacy and Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan
| | - Rajashri R Naik
- Pharmacological and Diagnostic Research Center, Faculty of Pharmacy and Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan
- Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan
| | - Hamdi Nsairat
- Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan
- Pharmacological and Diagnostic Research Center, Faculty of Pharmacy and Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan
| | - Sara Suboh
- Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan
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21
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Jadhav S, Yadav A. Phytoconstituents Based Nanomedicines for the Management of Diabetes: A Review. Pharm Nanotechnol 2023; 11:217-237. [PMID: 36654462 DOI: 10.2174/2211738511666230118095936] [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: 05/24/2022] [Revised: 09/13/2022] [Accepted: 10/12/2022] [Indexed: 01/19/2023]
Abstract
Diabetes mellitus (DM) is a life-threatening multifactorial metabolic syndrome that is still one of the most difficult unsolved health concerns. Different herbal drugs have been proposed to be useful in treating diabetes and its associated complications. Two major obstacles in plant extracts are their limited solubility and bioavailability of lipophilic bioactive components. Applying nanotechnology has opened new avenues to improve solubility, bioavailability, compliance, and efficacy by overcoming the pharmacokinetic and biopharmaceutical obstacles associated with herbal extracts and phytochemicals. Herbal nanomedicines can overcome the drawbacks of conventional therapy of DM, its complications like delayed wound healing, and also decrease the side effects of synthetic drugs. The targeted delivery of herbal nanoparticles employing nano-pumps, nanorobots, smart cells, and nanosized herbal medications is recognized today as one of the most far-reaching discoveries in the therapy of DM. This paper focuses on using nanotechnology and herbal therapies to manage diabetes effectively. The review provides a detailed and up-to-date overview of phytonanoformulations in treating diabetes and its consequences.
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Affiliation(s)
- Shailaja Jadhav
- Department of Pharmaceutics, Government College of Pharmacy, Karad, Shivaji University, Karad, 415004, India
| | - Adhikarao Yadav
- Department of Pharmaceutics, Government College of Pharmacy, Karad, Shivaji University, Karad, 415004, India
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22
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Peng B, Yang Y, Wu Z, Tan R, Pham TT, Yeo EYM, Pirisinu M, Jayasinghe MK, Pham TC, Liang K, Shyh-Chang N, Le MTN. Red blood cell extracellular vesicles deliver therapeutic siRNAs to skeletal muscles for treatment of cancer cachexia. Mol Ther 2023; 31:1418-1436. [PMID: 37016578 PMCID: PMC10188904 DOI: 10.1016/j.ymthe.2023.03.036] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 02/22/2023] [Accepted: 03/31/2023] [Indexed: 04/05/2023] Open
Abstract
Cancer cachexia is a multifactorial syndrome characterized by a significant loss of skeletal muscle, which negatively affects the quality of life. Inhibition of myostatin (Mstn), a negative regulator of skeletal muscle growth and differentiation, has been proven to preserve muscle mass in muscle atrophy diseases, including cachexia. However, myostatin inhibitors have repeatedly failed clinical trials because of modest therapeutic effects and side effects due to the poor efficiency and toxicity of existing delivery methods. Here, we describe a novel method for delivering Mstn siRNA to skeletal muscles using red blood cell-derived extracellular vesicles (RBCEVs) in a cancer cachectic mouse model. Our data show that RBCEVs are taken up by myofibers via intramuscular administration. Repeated intramuscular administrations with RBCEVs allowed the delivery of siRNAs, thereby inhibiting Mstn, increasing muscle growth, and preventing cachexia in cancer-bearing mice. We observed the same therapeutic effects when delivering siRNAs against malonyl-CoA decarboxylase, an enzyme driving dysfunctional fatty acid metabolism in skeletal muscles during cancer cachexia. We demonstrate that intramuscular siRNA delivery by RBCEVs is safe and non-inflammatory. Hence, this method is useful to reduce the therapeutic dose of siRNAs, to avoid toxicity and off-target effects caused by systemic administration of naked siRNAs at high doses.
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Affiliation(s)
- Boya Peng
- Department of Pharmacology and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; Department of Surgery, Immunology Program, Cancer Program and Nanomedicine Translational Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
| | - Yuqi Yang
- Department of Pharmacology and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; Department of Surgery, Immunology Program, Cancer Program and Nanomedicine Translational Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong 999077, China
| | - Zhiyuan Wu
- Department of Pharmacology and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; Department of Surgery, Immunology Program, Cancer Program and Nanomedicine Translational Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
| | - Rachel Tan
- Department of Pharmacology and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; Department of Surgery, Immunology Program, Cancer Program and Nanomedicine Translational Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
| | - Thach Tuan Pham
- Department of Pharmacology and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; Department of Surgery, Immunology Program, Cancer Program and Nanomedicine Translational Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
| | - Eric Yew Meng Yeo
- Department of Pharmacology and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; Department of Surgery, Immunology Program, Cancer Program and Nanomedicine Translational Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
| | - Marco Pirisinu
- Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong 999077, China
| | - Migara Kavishka Jayasinghe
- Department of Pharmacology and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; Department of Surgery, Immunology Program, Cancer Program and Nanomedicine Translational Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
| | - Tin Chanh Pham
- Department of Pharmacology and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; Department of Surgery, Immunology Program, Cancer Program and Nanomedicine Translational Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong 999077, China
| | - Kun Liang
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, China
| | - Ng Shyh-Chang
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, China.
| | - Minh T N Le
- Department of Pharmacology and Institute for Digital Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; Department of Surgery, Immunology Program, Cancer Program and Nanomedicine Translational Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore.
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23
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Ashraf M, Ahammad SZ, Chakma S. Advancements in the dominion of fate and transport of pharmaceuticals and personal care products in the environment-a bibliometric study. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:64313-64341. [PMID: 37067715 PMCID: PMC10108824 DOI: 10.1007/s11356-023-26796-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 03/30/2023] [Indexed: 05/11/2023]
Abstract
The study on the fate and transport of Pharmaceuticals and Personal Care Products, PPCPs (FTP) in the environment, has received particular attention for over two decades. The PPCPs threaten ecology and human health even at low concentrations due to their synergistic effects and long-range transport. The research aims to provide an inclusive map of the scientific background of FTP research over the last 25 years, from 1996 to 2020, to identify the main characteristics, evolution, salient research themes, trends, and research hotspots in the field of interest. Bibliometric networks were synthesized and analyzed for 577 journal articles extracted from the Scopus database. Consequently, seven major themes of FTP research were identified as follows: (i) PPCPs category; (ii) hazardous effects; (iii) occurrence of PPCPs; (iv) PPCPs in organisms; (v) remediation; (vi) FTP-governing processes; and (vii) assessment in the environment. The themes gave an in-depth picture of the sources of PPCPs and their transport and fate processes in the environment, which originated from sewage treatment plants and transported further to sediment/soils/groundwater/oceans that act as the PPCPs' major sink. The article provided a rigorous analysis of the research landscape in the FTP study conducted during the specified years. The prominent research themes, content analysis, and research hotspots identified in the study may serve as the basis of real-time guidance to lead future research areas and a prior review for policymakers and practitioners.
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Affiliation(s)
- Maliha Ashraf
- School of Interdisciplinary Research, Indian Institute of Technology, Delhi, India.
| | - Shaikh Ziauddin Ahammad
- Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, Delhi, India
| | - Sumedha Chakma
- Department of Civil Engineering, Indian Institute of Technology, Delhi, India
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24
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Zhang X, Misra SK, Moitra P, Zhang X, Jeong SJ, Stitham J, Rodriguez-Velez A, Park A, Yeh YS, Gillanders WE, Fan D, Diwan A, Cho J, Epelman S, Lodhi IJ, Pan D, Razani B. Use of acidic nanoparticles to rescue macrophage lysosomal dysfunction in atherosclerosis. Autophagy 2023; 19:886-903. [PMID: 35982578 PMCID: PMC9980706 DOI: 10.1080/15548627.2022.2108252] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 07/23/2022] [Accepted: 07/25/2022] [Indexed: 12/19/2022] Open
Abstract
Dysfunction in the macrophage lysosomal system including reduced acidity and diminished degradative capacity is a hallmark of atherosclerosis, leading to blunted clearance of excess cellular debris and lipids in plaques and contributing to lesion progression. Devising strategies to rescue this macrophage lysosomal dysfunction is a novel therapeutic measure. Nanoparticles have emerged as an effective platform to both target specific tissues and serve as drug delivery vehicles. In most cases, administered nanoparticles are taken up non-selectively by the mononuclear phagocyte system including monocytes/macrophages leading to the undesirable degradation of cargo in lysosomes. We took advantage of this default route to target macrophage lysosomes to rectify their acidity in disease states such as atherosclerosis. Herein, we develop and test two commonly used acidic nanoparticles, poly-lactide-co-glycolic acid (PLGA) and polylactic acid (PLA), both in vitro and in vivo. Our results in cultured macrophages indicate that the PLGA-based nanoparticles are the most effective at trafficking to and enhancing acidification of lysosomes. PLGA nanoparticles also provide functional benefits including enhanced lysosomal degradation, promotion of macroautophagy/autophagy and protein aggregate removal, and reduced apoptosis and inflammasome activation. We demonstrate the utility of this system in vivo, showing nanoparticle accumulation in, and lysosomal acidification of, macrophages in atherosclerotic plaques. Long-term administration of PLGA nanoparticles results in significant reductions in surrogates of plaque complexity with reduced apoptosis, necrotic core formation, and cytotoxic protein aggregates and increased fibrous cap formation. Taken together, our data support the use of acidic nanoparticles to rescue macrophage lysosomal dysfunction in the treatment of atherosclerosis.Abbreviations: BCA: brachiocephalic arteries; FACS: fluorescence activated cell sorting; FITC: fluorescein-5-isothiocyanatel; IL1B: interleukin 1 beta; LAMP: lysosomal associated membrane protein; LIPA/LAL: lipase A, lysosomal acid type; LSDs: lysosomal storage disorders; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MFI: mean fluorescence intensity; MPS: mononuclear phagocyte system; PEGHDE: polyethylene glycol hexadecyl ether; PLA: polylactic acid; PLGA: poly-lactide-co-glycolic acid; SQSTM1/p62: sequestosome 1.
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Affiliation(s)
- Xiangyu Zhang
- Cardiovascular Division, Washington University, St. Louis, MO, USA
| | - Santosh Kumar Misra
- Department of Bioengineering, University of Illinois at Urbana Champaign, IL, USA
| | - Parikshit Moitra
- Departments of Diagnostic Radiology and Nuclear Medicine and Pediatrics, Baltimore, Maryland, USA
- Department of Nuclear Engineering, The Pennsylvania State University, University Park, Pennsylvania16802, USA
| | - Xiuli Zhang
- Department of Surgery, Washington University, St. Louis, MO, USA
| | - Se-Jin Jeong
- Cardiovascular Division, Washington University, St. Louis, MO, USA
| | - Jeremiah Stitham
- Cardiovascular Division, Washington University, St. Louis, MO, USA
- Division of Endocrinology, Metabolism, and Lipid Research, St. Louis, MO, USA
| | | | - Arick Park
- Cardiovascular Division, Washington University, St. Louis, MO, USA
| | - Yu-Sheng Yeh
- Cardiovascular Division, Washington University, St. Louis, MO, USA
| | | | - Daping Fan
- Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC, USA
| | - Abhinav Diwan
- Cardiovascular Division, Washington University, St. Louis, MO, USA
- John Cochran Division, VA Medical Center, St. Louis, MO, USA
| | - Jaehyung Cho
- Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
- Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA
| | - Slava Epelman
- Peter Munk Cardiac Center, Toronto General Hospital Research Institute, University Health Network, Ted Rogers Centre for Heart Research, University of Toronto, Toronto, Ontario, Canada
| | - Irfan J. Lodhi
- Division of Endocrinology, Metabolism, and Lipid Research, St. Louis, MO, USA
| | - Dipanjan Pan
- Department of Bioengineering, University of Illinois at Urbana Champaign, IL, USA
- Departments of Diagnostic Radiology and Nuclear Medicine and Pediatrics, Baltimore, Maryland, USA
- Department of Nuclear Engineering, The Pennsylvania State University, University Park, Pennsylvania16802, USA
| | - Babak Razani
- Cardiovascular Division, Washington University, St. Louis, MO, USA
- John Cochran Division, VA Medical Center, St. Louis, MO, USA
- Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA
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25
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Horvath D, Basler M. PLGA Particles in Immunotherapy. Pharmaceutics 2023; 15:pharmaceutics15020615. [PMID: 36839937 PMCID: PMC9965784 DOI: 10.3390/pharmaceutics15020615] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 02/06/2023] [Accepted: 02/07/2023] [Indexed: 02/16/2023] Open
Abstract
Poly(lactic-co-glycolic acid) (PLGA) particles are a widely used and extensively studied drug delivery system. The favorable properties of PLGA such as good bioavailability, controlled release, and an excellent safety profile due to the biodegradable polymer backbone qualified PLGA particles for approval by the authorities for the application as a drug delivery platform in humas. In recent years, immunotherapy has been established as a potent treatment option for a variety of diseases. However, immunomodulating drugs rely on targeted delivery to specific immune cell subsets and are often rapidly eliminated from the system. Loading of PLGA particles with drugs for immunotherapy can protect the therapeutic compounds from premature degradation, direct the drug delivery to specific tissues or cells, and ensure sustained and controlled drug release. These properties present PLGA particles as an ideal platform for immunotherapy. Here, we review recent advances of particulate PLGA delivery systems in the application for immunotherapy in the fields of allergy, autoimmunity, infectious diseases, and cancer.
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Affiliation(s)
- Dennis Horvath
- Division of Immunology, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany
- Centre for the Advanced Study of Collective Behaviour, University of Konstanz, D-78457 Konstanz, Germany
| | - Michael Basler
- Division of Immunology, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany
- Biotechnology Institute Thurgau (BITg) at the University of Konstanz, CH-8280 Kreuzlingen, Switzerland
- Correspondence:
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Hughes KA, Misra B, Maghareh M, Bobbala S. Use of stimulatory responsive soft nanoparticles for intracellular drug delivery. NANO RESEARCH 2023; 16:6974-6990. [PMID: 36685637 PMCID: PMC9840428 DOI: 10.1007/s12274-022-5267-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 10/30/2022] [Accepted: 10/31/2022] [Indexed: 05/24/2023]
Abstract
Drug delivery has made tremendous advances in the last decade. Targeted therapies are increasingly common, with intracellular delivery highly impactful and sought after. Intracellular drug delivery systems have limitations due to imprecise and non-targeted release profiles. One way this can be addressed is through using stimuli-responsive soft nanoparticles, which contain materials with an organic backbone such as lipids and polymers. The choice of biomaterial is essential for soft nanoparticles to be responsive to internal or external stimuli. The nanoparticle must retain its integrity and payload in non-targeted physiological conditions while responding to particular intracellular environments where payload release is desired. Multiple internal and external factors could stimulate the intracellular release of drugs from nanoparticles. Internal stimuli include pH, oxidation, and enzymes, while external stimuli include ultrasound, light, electricity, and magnetic fields. Stimulatory responsive soft nanoparticulate systems specifically utilized to modulate intracellular delivery of drugs are explored in this review.
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Affiliation(s)
- Krystal A. Hughes
- Department of Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV 26505 USA
| | - Bishal Misra
- Department of Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV 26505 USA
| | - Maryam Maghareh
- Department of Clinical Pharmacy, West Virginia University School of Pharmacy, Morgantown, WV 26505 USA
| | - Sharan Bobbala
- Department of Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV 26505 USA
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27
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Jo S, Sun IC, Ahn CH, Lee S, Kim K. Recent Trend of Ultrasound-Mediated Nanoparticle Delivery for Brain Imaging and Treatment. ACS APPLIED MATERIALS & INTERFACES 2023; 15:120-137. [PMID: 35184560 DOI: 10.1021/acsami.1c22803] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
In view of the fact that the blood-brain barrier (BBB) prevents the transport of imaging probes and therapeutic agents to the brain and thus hinders the diagnosis and treatment of brain-related disorders, methods of circumventing this problem (e.g., ultrasound-mediated nanoparticle delivery) have drawn much attention. Among the related techniques, focused ultrasound (FUS) is a favorite means of enhancing drug delivery via transient BBB opening. Photoacoustic brain imaging relies on the conversion of light into heat and the detection of ultrasound signals from contrast agents, offering the benefits of high resolution and large penetration depth. The extensive versatility and adjustable physicochemical properties of nanoparticles make them promising therapeutic agents and imaging probes, allowing for successful brain imaging and treatment through the combined action of ultrasound and nanoparticulate agents. FUS-induced BBB opening enables nanoparticle-based drug delivery systems to efficiently access the brain. Moreover, photoacoustic brain imaging using nanoparticle-based contrast agents effectively visualizes brain morphologies or diseases. Herein, we review the progress in the simultaneous use of nanoparticles and ultrasound in brain research, revealing the potential of ultrasound-mediated nanoparticle delivery for the effective diagnosis and treatment of brain disorders.
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Affiliation(s)
- SeongHoon Jo
- Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 5, Hwarang-ro, Seongbuk-gu, Seoul 02792, Republic of Korea
- Research Institute of Advanced Materials (RIAM), Department of Materials Science and Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul08826, Republic of Korea
| | - In-Cheol Sun
- Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 5, Hwarang-ro, Seongbuk-gu, Seoul 02792, Republic of Korea
| | - Cheol-Hee Ahn
- Research Institute of Advanced Materials (RIAM), Department of Materials Science and Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul08826, Republic of Korea
| | - Sangmin Lee
- Department of Pharmacy, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul02447, Korea
| | - Kwangmeyung Kim
- Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 5, Hwarang-ro, Seongbuk-gu, Seoul 02792, Republic of Korea
- KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea
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Joseph TM, Kallingal A, Suresh AM, Mahapatra DK, Hasanin MS, Haponiuk J, Thomas S. 3D printing of polylactic acid: recent advances and opportunities. THE INTERNATIONAL JOURNAL, ADVANCED MANUFACTURING TECHNOLOGY 2023; 125:1015-1035. [PMID: 36644783 PMCID: PMC9822698 DOI: 10.1007/s00170-022-10795-y] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 12/29/2022] [Indexed: 05/12/2023]
Abstract
Bio-based polymers are a class of polymers made by living organisms, a few of them known and commercialized yet. Due to poor mechanical strength and economic constraints, they have not yet seen the extensive application. Instead, they have been an appropriate candidate for biological applications. Growing consumer knowledge of the environmental effect of polymers generated from petrochemical sources and a worldwide transition away from plastics with a lifespan of hundreds of years has resulted in greater interest in such hitherto unattainable sectors. Bio-based polymers come in various forms, including direct or "drop-in" replacements for their petrochemical counterparts with nearly identical properties or completely novel polymers that were previously unavailable, such as polylactide. Few of these bio-based polymers offer significantly improved technical specifications than their alternatives. Polylactic acid (PLA) has been well known in the last decade as a biodegradable thermoplastic source for use in 3DP by the "fused deposition modeling" method. The PLA market is anticipated to accomplish 5.2 billion US dollars in 2020 for its industrial usage. Conversely, 3DP is one of the emerging technologies with immense economic potential in numerous sectors where PLA is one of the critical options as the polymer source due to its environmentally friendly nature, glossiness, multicolor appearance, and ease of printing. The chemical structure, manufacturing techniques, standard features, and current market situation of PLA were examined in this study. This review looks at the process of 3DP that uses PLA filaments in extrusion-based 3DP technologies in particular. Several recent articles describing 3D-printed PLA items have been highlighted.
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Affiliation(s)
- Tomy Muringayil Joseph
- Department of Polymers Technology, Faculty of Chemistry, Gdańsk University of Technology, G. Narutowicza 11/12, 80-233 Gdańsk, Poland
| | - Anoop Kallingal
- Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, 80-233 Gdansk, Poland
| | - Akshay Maniyeri Suresh
- Laboratory of Bacterial Genetics, Faculty of Chemistry, Gdansk University of Technology, 80-233 Gdansk, Poland
| | - Debarshi Kar Mahapatra
- Department of Pharmaceutical Chemistry, Dadasaheb Balpande College of Pharmacy, Nagpur, 440037 Maharashtra India
| | - Mohamed S. Hasanin
- Department of Polymers Technology, Faculty of Chemistry, Gdańsk University of Technology, G. Narutowicza 11/12, 80-233 Gdańsk, Poland
- Cellulose and Paper Department, National Research Centre, Dokki, Cairo, 12622 Egypt
| | - Józef Haponiuk
- Department of Polymers Technology, Faculty of Chemistry, Gdańsk University of Technology, G. Narutowicza 11/12, 80-233 Gdańsk, Poland
| | - Sabu Thomas
- International and Inter University Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam, 686560 India
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Liu M, Thijssen S, Hennink WE, Garssen J, van Nostrum CF, Willemsen LM. Oral pretreatment with β-lactoglobulin derived peptide and CpG co-encapsulated in PLGA nanoparticles prior to sensitizations attenuates cow's milk allergy development in mice. Front Immunol 2023; 13:1053107. [PMID: 36703973 PMCID: PMC9872660 DOI: 10.3389/fimmu.2022.1053107] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Accepted: 12/19/2022] [Indexed: 01/07/2023] Open
Abstract
Cow's milk allergy is a common food allergy among infants. Improved hygiene conditions and loss of microbial diversity are associated with increased risk of allergy development. The intestinal immune system is essential for oral tolerance induction. In this respect, bacterial CpG DNA is known to drive Th1 and regulatory T-cell (Treg) development via Toll-Like-Receptor 9 (TLR-9) signaling, skewing away from the allergic Th2 phenotype. We aimed to induce allergen specific tolerance via oral delivery of poly (lactic-co-glycolic acid) nanoparticles (NP) co-encapsulated with a selected β-lactoglobulin derived peptide (BLG-Pep) and TLR-9 ligand CpG oligodeoxynucleotide (CpG). In vivo, 3-4-week-old female C3H/HeOuJ mice housed in individually ventilated cages received 6-consecutive-daily gavages of either PBS, whey, BLG-Pep/NP, CpG/NP, a mixture of BLG-Pep/NP plus CpG/NP or co-encapsulated BLG-Pep+CpG/NP, before 5-weekly oral sensitizations with whey plus cholera toxin (CT) or only CT (sham) and were challenged with whey 5 days after the last sensitization. The co-encapsulated BLG-Pep+CpG/NP pretreatment, but not BLG-Pep/NP, CpG/NP or the mixture of BLG-Pep/NP plus CpG/NP, prevented the whey-induced allergic skin reactivity and prevented rise in serum BLG-specific IgE compared to whey-sensitized mice. Importantly, co-encapsulated BLG-Pep+CpG/NP pretreatment reduced dendritic cell (DC) activation and lowered the frequencies of PD-L1+ DC in the mesenteric lymph nodes compared to whey-sensitized mice. By contrast, co-encapsulated BLG-Pep+CpG/NP pretreatment increased the frequency of splenic PD-L1+ DC compared to the BLG-Pep/NP plus CpG/NP recipients, in association with lower Th2 development and increased Treg/Th2 and Th1/Th2 ratios in the spleen. Oral administration of PLGA NP co-encapsulated with BLG-Pep and CpG prevented rise in serum BLG-specific IgE and symptom development while lowering splenic Th2 cell frequency in these mice which were kept under strict hygienic conditions.
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Affiliation(s)
- Mengshan Liu
- Division of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands,Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - Suzan Thijssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - Wim E. Hennink
- Division of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands,Department of Immunology, Nutricia Research B.V., Utrecht, Netherlands
| | - Cornelus F. van Nostrum
- Division of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - Linette E. M. Willemsen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands,*Correspondence: Linette E. M. Willemsen,
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Sohrabi M, Babaei Z, Haghpanah V, Larijani B, Abbasi A, Mahdavi M. Recent advances in gene therapy-based cancer monotherapy and synergistic bimodal therapy using upconversion nanoparticles: Structural and biological aspects. Biomed Pharmacother 2022; 156:113872. [DOI: 10.1016/j.biopha.2022.113872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 10/06/2022] [Accepted: 10/13/2022] [Indexed: 11/02/2022] Open
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Cytokine Therapy Combined with Nanomaterials Participates in Cancer Immunotherapy. Pharmaceutics 2022; 14:pharmaceutics14122606. [PMID: 36559100 PMCID: PMC9788370 DOI: 10.3390/pharmaceutics14122606] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 11/14/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
Immunotherapy has gradually become an emerging treatment modality for tumors after surgery, radiotherapy, and chemotherapy. Cytokine therapy is a promising treatment for cancer immunotherapy. Currently, there are many preclinical theoretical bases to support this treatment strategy and a variety of cytokines in clinical trials. When cytokines were applied to tumor immunotherapy, it was found that the efficacy was not satisfactory. As research on tumor immunity has deepened, the role of cytokines in the tumor microenvironment has been further explored. Meanwhile, the study of nanomaterials in drug delivery has been fully developed in the past 20 years. Researchers have begun to think about the possibility of combining cytokine therapy with nanomaterials. Herein, we briefly review various nano-delivery systems that can directly deliver cytokines or regulate the expression of cytokines in tumor cells for cancer immunotherapy. We further discussed the feasibility of the combination of various therapies. We looked forward to the main challenges, opportunities, and prospects of tumor immunotherapy with multiple cytokines and a nano-delivery system.
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Aptamer-Functionalized Nanoparticles Mediate PD-L1 siRNA Delivery for Effective Gene Silencing in Triple-Negative Breast Cancer Cells. Pharmaceutics 2022; 14:pharmaceutics14102225. [PMID: 36297659 PMCID: PMC9609037 DOI: 10.3390/pharmaceutics14102225] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 10/03/2022] [Accepted: 10/12/2022] [Indexed: 11/21/2022] Open
Abstract
Small interfering RNA (siRNA) therapies require effective delivery vehicles capable of carrying the siRNA cargo into target cells. To achieve tumor-targeting, a drug delivery system would have to incorporate ligands that specifically bind to receptors expressed on cancer cells to function as portals via receptor-mediated endocytosis. Cell-targeting and internalizing aptamers are the most suitable ligands for functionalization of drug-loaded nanocarriers. Here, we designed a novel aptamer-based platform for the active delivery of siRNA targeting programmed cell death-ligand 1 (PD-L1) to triple-negative breast cancer (TNBC) cells. The generated nanovectors consist of PLGA-based polymeric nanoparticles, which were loaded with PD-L1 siRNA and conjugated on their surface with a new RNA aptamer, specific for TNBC and resistant to nucleases. In vitro results demonstrated that these aptamer-conjugated nanoparticles promote siRNA uptake specifically into TNBC MDA-MB-231 and BT-549 target cells, along with its endosomal release, without recognizing non-TNBC BT-474 breast cancer cells. Their efficiency resulted in an almost complete suppression of PD-L1 expression as early as 90 min of cell treatment. This research provides a rational strategy for optimizing siRNA delivery systems for TNBC treatments.
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Zhou R, Zhao D, Beeraka NM, Wang X, Lu P, Song R, Chen K, Liu J. Novel Implications of Nanoparticle-Enhanced Radiotherapy and Brachytherapy: Z-Effect and Tumor Hypoxia. Metabolites 2022; 12:943. [PMID: 36295845 PMCID: PMC9612299 DOI: 10.3390/metabo12100943] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 09/28/2022] [Accepted: 09/30/2022] [Indexed: 10/29/2023] Open
Abstract
Radiotherapy and internal radioisotope therapy (brachytherapy) induce tumor cell death through different molecular signaling pathways. However, these therapies in cancer patients are constrained by dose-related adverse effects and local discomfort due to the prolonged exposure to the surrounding tissues. Technological advancements in nanotechnology have resulted in synthesis of high atomic elements such as nanomaterials, which can be used as radiosensitizers due to their photoelectric characteristics. The aim of this review is to elucidate the effects of novel nanomaterials in the field of radiation oncology to ameliorate dose-related toxicity through the application of ideal nanoparticle-based radiosensitizers such as Au (gold), Bi (bismuth), and Lu (Lutetium-177) for enhancing cytotoxic effects of radiotherapy via the high-Z effect. In addition, we discuss the role of nanoparticle-enhanced radiotherapy in alleviating tumor hypoxia through the nanodelivery of genes/drugs and other functional anticancer molecules. The implications of engineered nanoparticles in preclinical and clinical studies still need to be studied in order to explore potential mechanisms for radiosensitization by minimizing tumor hypoxia, operational/logistic complications and by overcoming tumor heterogeneity in radiotherapy/brachytherapy.
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Affiliation(s)
- Runze Zhou
- Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
| | - Di Zhao
- Endocrinology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
| | - Narasimha M. Beeraka
- Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
- Department of Pharmaceutical Chemistry, Jagadguru Sri Shivarathreeswara Academy of Higher Education and Research (JSS AHER), Jagadguru Sri Shivarathreeswara College of Pharmacy, Mysuru 570015, India
- Department of Human Anatomy, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119991 Moscow, Russia
| | - Xiaoyan Wang
- Endocrinology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
| | - Pengwei Lu
- Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
| | - Ruixia Song
- Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
| | - Kuo Chen
- Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
| | - Junqi Liu
- Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
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Warner JB, Guenthner SC, Hardesty JE, McClain CJ, Warner DR, Kirpich IA. Liver-specific drug delivery platforms: Applications for the treatment of alcohol-associated liver disease. World J Gastroenterol 2022; 28:5280-5299. [PMID: 36185629 PMCID: PMC9521517 DOI: 10.3748/wjg.v28.i36.5280] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 08/16/2022] [Accepted: 09/06/2022] [Indexed: 02/06/2023] Open
Abstract
Alcohol-associated liver disease (ALD) is a common chronic liver disease and major contributor to liver disease-related deaths worldwide. Despite its pre-valence, there are few effective pharmacological options for the severe stages of this disease. While much pre-clinical research attention is paid to drug development in ALD, many of these experimental therapeutics have limitations such as poor pharmacokinetics, poor efficacy, or off-target side effects due to systemic administration. One means of addressing these limitations is through liver-targeted drug delivery, which can be accomplished with different platforms including liposomes, polymeric nanoparticles, exosomes, bacteria, and adeno-associated viruses, among others. These platforms allow drugs to target the liver passively or actively, thereby reducing systemic circulation and increasing the ‘effective dose’ in the liver. While many studies, some clinical, have applied targeted delivery systems to other liver diseases such as viral hepatitis or hepatocellular carcinoma, only few have investigated their efficacy in ALD. This review provides basic information on these liver-targeting drug delivery platforms, including their benefits and limitations, and summarizes the current research efforts to apply them to the treatment of ALD in rodent models. We also discuss gaps in knowledge in the field, which when addressed, may help to increase the efficacy of novel therapies and better translate them to humans.
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Affiliation(s)
- Jeffrey Barr Warner
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States
| | - Steven Corrigan Guenthner
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
| | - Josiah Everett Hardesty
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
| | - Craig James McClain
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Alcohol Research Center, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Hepatobiology and Toxicology Center, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Veterans Health Administration, Robley Rex Veterans Medical Center, Louisville, KY 40206, United States
| | - Dennis Ray Warner
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
| | - Irina Andreyevna Kirpich
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Alcohol Research Center, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Hepatobiology and Toxicology Center, University of Louisville School of Medicine, Louisville, KY 40202, United States
- Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, United States
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Gao L, Li J, Song T. Poly lactic-co-glycolic acid-based nanoparticles as delivery systems for enhanced cancer immunotherapy. Front Chem 2022; 10:973666. [PMID: 36046731 PMCID: PMC9420966 DOI: 10.3389/fchem.2022.973666] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 07/19/2022] [Indexed: 12/12/2022] Open
Abstract
Cancer has emerged as one of the most severe diseases in modern times, various therapies have advanced remarkably in recent decades. Unlike the direct therapeutic targeting tumor cells, immunotherapy is a promising strategy that stimulate the immune system. In cancer immunotherapy, polymeric-based nanoparticles can serve as deliver systems for antigens and immunostimulatory molecules, and they have attracted increasing attention and revolutionized cancer therapy. Poly (lactic-co-glycolic acid) (PLGA) is the most frequently used clinically approved biodegradable polymer and has a broad scope of modification of its inherent properties. Recent advances in PLGA based drug delivery systems in cancer immunotherapy have been described in this mini review, with special emphasis on cancer vaccines and tumor microenvironment modulation.
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Affiliation(s)
- Lei Gao
- The Second Hospital of Tianjin Medical University, Tianjin, China
- *Correspondence: Lei Gao, ; Jing Li,
| | - Jing Li
- The Second Hospital of Tianjin Medical University, Tianjin, China
- *Correspondence: Lei Gao, ; Jing Li,
| | - Tianhang Song
- State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin, China
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Wang S, Cheng K, Chen K, Xu C, Ma P, Dang G, Yang Y, Lei Q, Huang H, Yu Y, Fang Y, Tang Q, Jiang N, Miao H, Liu F, Zhao X, Li N. Nanoparticle-based medicines in clinical cancer therapy. NANO TODAY 2022; 45:101512. [DOI: 10.1016/j.nantod.2022.101512] [Citation(s) in RCA: 77] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2024]
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Rodríguez F, Caruana P, De la Fuente N, Español P, Gámez M, Balart J, Llurba E, Rovira R, Ruiz R, Martín-Lorente C, Corchero JL, Céspedes MV. Nano-Based Approved Pharmaceuticals for Cancer Treatment: Present and Future Challenges. Biomolecules 2022; 12:biom12060784. [PMID: 35740909 PMCID: PMC9221343 DOI: 10.3390/biom12060784] [Citation(s) in RCA: 101] [Impact Index Per Article: 33.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 05/31/2022] [Accepted: 06/02/2022] [Indexed: 02/01/2023] Open
Abstract
Cancer is one of the main causes of death worldwide. To date, and despite the advances in conventional treatment options, therapy in cancer is still far from optimal due to the non-specific systemic biodistribution of antitumor agents. The inadequate drug concentrations at the tumor site led to an increased incidence of multiple drug resistance and the appearance of many severe undesirable side effects. Nanotechnology, through the development of nanoscale-based pharmaceuticals, has emerged to provide new and innovative drugs to overcome these limitations. In this review, we provide an overview of the approved nanomedicine for cancer treatment and the rationale behind their designs and applications. We also highlight the new approaches that are currently under investigation and the perspectives and challenges for nanopharmaceuticals, focusing on the tumor microenvironment and tumor disseminate cells as the most attractive and effective strategies for cancer treatments.
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Affiliation(s)
- Francisco Rodríguez
- Grup d’Oncologia Ginecològica i Peritoneal, Institut d’Investigacions Biomédiques Sant Pau, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain; (F.R.); (P.C.); (R.R.)
| | - Pablo Caruana
- Grup d’Oncologia Ginecològica i Peritoneal, Institut d’Investigacions Biomédiques Sant Pau, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain; (F.R.); (P.C.); (R.R.)
| | - Noa De la Fuente
- Servicio de Cirugía General y del Aparato Digestivo, Hospital HM Rosaleda, 15701 Santiago de Compostela, Spain;
| | - Pía Español
- Department of Obstetrics and Gynecology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, 08041 Barcelona, Spain; (P.E.); (E.L.); (R.R.)
| | - María Gámez
- Department of Pharmacy, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain;
| | - Josep Balart
- Department of Radiation Oncology, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain;
| | - Elisa Llurba
- Department of Obstetrics and Gynecology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, 08041 Barcelona, Spain; (P.E.); (E.L.); (R.R.)
| | - Ramón Rovira
- Department of Obstetrics and Gynecology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, 08041 Barcelona, Spain; (P.E.); (E.L.); (R.R.)
| | - Raúl Ruiz
- Grup d’Oncologia Ginecològica i Peritoneal, Institut d’Investigacions Biomédiques Sant Pau, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain; (F.R.); (P.C.); (R.R.)
| | - Cristina Martín-Lorente
- Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain;
| | - José Luis Corchero
- Institut de Biotecnologia i de Biomedicina and CIBER-BBN, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain
- Correspondence: (J.L.C.); (M.V.C.); Tel.: +34-93-5812148 (J.L.C.); +34-93-400000 (ext. 1427) (M.V.C.)
| | - María Virtudes Céspedes
- Grup d’Oncologia Ginecològica i Peritoneal, Institut d’Investigacions Biomédiques Sant Pau, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain; (F.R.); (P.C.); (R.R.)
- Correspondence: (J.L.C.); (M.V.C.); Tel.: +34-93-5812148 (J.L.C.); +34-93-400000 (ext. 1427) (M.V.C.)
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Polyketal-based nanocarriers: A new class of stimuli-responsive delivery systems for therapeutic applications. Eur Polym J 2022. [DOI: 10.1016/j.eurpolymj.2022.111290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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PLGA particle vaccination elicits resident memory CD8 T cells protecting from tumors and infection. Eur J Pharm Sci 2022; 175:106209. [DOI: 10.1016/j.ejps.2022.106209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 05/02/2022] [Accepted: 05/12/2022] [Indexed: 11/20/2022]
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Bidooki SH, Alejo T, Sánchez-Marco J, Martínez-Beamonte R, Abuobeid R, Burillo JC, Lasheras R, Sebastian V, Rodríguez-Yoldi MJ, Arruebo M, Osada J. Squalene Loaded Nanoparticles Effectively Protect Hepatic AML12 Cell Lines against Oxidative and Endoplasmic Reticulum Stress in a TXNDC5-Dependent Way. Antioxidants (Basel) 2022; 11:antiox11030581. [PMID: 35326231 PMCID: PMC8945349 DOI: 10.3390/antiox11030581] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/15/2022] [Accepted: 03/16/2022] [Indexed: 01/27/2023] Open
Abstract
Virgin olive oil, the main source of fat in the Mediterranean diet, contains a substantial amount of squalene which possesses natural antioxidant properties. Due to its highly hydrophobic nature, its bioavailability is reduced. In order to increase its delivery and potentiate its actions, squalene has been loaded into PLGA nanoparticles (NPs). The characterization of the resulting nanoparticles was assessed by electron microscopy, dynamic light scattering, zeta potential and high-performance liquid chromatography. Reactive oxygen species (ROS) generation and cell viability assays were carried out in AML12 (alpha mouse liver cell line) and a TXNDC5-deficient AML12 cell line (KO), which was generated by CRISPR/cas9 technology. According to the results, squalene was successfully encapsulated in PLGA NPs, and had rapid and efficient cellular uptake at 30 µM squalene concentration. Squalene reduced ROS in AML12, whereas ROS levels increased in KO cells and improved cell viability in both when subjected to oxidative stress by significant induction of Gpx4. Squalene enhanced cell viability in ER-induced stress by decreasing Ern1 or Eif2ak3 expressions. In conclusion, TXNDC5 shows a crucial role in regulating ER-induced stress through different signaling pathways, and squalene protects mouse hepatocytes from oxidative and endoplasmic reticulum stresses by several molecular mechanisms depending on TXNDC5.
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Affiliation(s)
- Seyed Hesamoddin Bidooki
- Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de Zaragoza, E-50013 Zaragoza, Spain; (S.H.B.); (J.S.-M.); (R.M.-B.); (R.A.)
| | - Teresa Alejo
- Departamento de Ingeniería Química y Tecnologías del Medio Ambiente, Universidad de Zaragoza, E-50018 Zaragoza, Spain; (T.A.); (V.S.); (M.A.)
- Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, E-50009 Zaragoza, Spain
| | - Javier Sánchez-Marco
- Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de Zaragoza, E-50013 Zaragoza, Spain; (S.H.B.); (J.S.-M.); (R.M.-B.); (R.A.)
| | - Roberto Martínez-Beamonte
- Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de Zaragoza, E-50013 Zaragoza, Spain; (S.H.B.); (J.S.-M.); (R.M.-B.); (R.A.)
- Instituto Agroalimentario de Aragón, CITA-Universidad de Zaragoza, E-50013 Zaragoza, Spain;
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain
| | - Roubi Abuobeid
- Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de Zaragoza, E-50013 Zaragoza, Spain; (S.H.B.); (J.S.-M.); (R.M.-B.); (R.A.)
| | - Juan Carlos Burillo
- Laboratorio Agroambiental, Servicio de Seguridad Agroalimentaria de la Dirección General de Alimentación y Fomento Agroalimentario, Gobierno de Aragón, E-50059 Zaragoza, Spain; (J.C.B.); (R.L.)
| | - Roberto Lasheras
- Laboratorio Agroambiental, Servicio de Seguridad Agroalimentaria de la Dirección General de Alimentación y Fomento Agroalimentario, Gobierno de Aragón, E-50059 Zaragoza, Spain; (J.C.B.); (R.L.)
| | - Victor Sebastian
- Departamento de Ingeniería Química y Tecnologías del Medio Ambiente, Universidad de Zaragoza, E-50018 Zaragoza, Spain; (T.A.); (V.S.); (M.A.)
- Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, E-50009 Zaragoza, Spain
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain
| | - María J. Rodríguez-Yoldi
- Instituto Agroalimentario de Aragón, CITA-Universidad de Zaragoza, E-50013 Zaragoza, Spain;
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain
- Departamento de Farmacología, Fisiología, Medicina Legal y Forense, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de Zaragoza, E-50013 Zaragoza, Spain
| | - Manuel Arruebo
- Departamento de Ingeniería Química y Tecnologías del Medio Ambiente, Universidad de Zaragoza, E-50018 Zaragoza, Spain; (T.A.); (V.S.); (M.A.)
- Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, E-50009 Zaragoza, Spain
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III, E-28029 Madrid, Spain
| | - Jesús Osada
- Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de Zaragoza, E-50013 Zaragoza, Spain; (S.H.B.); (J.S.-M.); (R.M.-B.); (R.A.)
- Instituto Agroalimentario de Aragón, CITA-Universidad de Zaragoza, E-50013 Zaragoza, Spain;
- Departamento de Farmacología, Fisiología, Medicina Legal y Forense, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón-Universidad de Zaragoza, E-50013 Zaragoza, Spain
- Correspondence: ; Tel.: +34-976-761-644; Fax: +34-976-761-612
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Jiang L, Luo J, Hong D, Guo S, Wang S, Zhou B, Zhou S, Ge J. Recent Advances of Poly(lactic‐co‐glycolic acid)‐Based Nanoparticles for Tumor‐Targeted Drug Delivery. ChemistrySelect 2022. [DOI: 10.1002/slct.202103524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Linye Jiang
- Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering Zhejiang University of Technology Hangzhou 310014 China
| | - Jie Luo
- Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering Zhejiang University of Technology Hangzhou 310014 China
| | - Dawei Hong
- Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering Zhejiang University of Technology Hangzhou 310014 China
| | - Shuhong Guo
- Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering Zhejiang University of Technology Hangzhou 310014 China
| | - Shuyi Wang
- Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering Zhejiang University of Technology Hangzhou 310014 China
| | - Bizhong Zhou
- Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering Zhejiang University of Technology Hangzhou 310014 China
| | - Shiyu Zhou
- Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering Zhejiang University of Technology Hangzhou 310014 China
| | - Jingyan Ge
- Key Laboratory of Bioorganic Synthesis of Zhejiang Province College of Biotechnology and Bioengineering Zhejiang University of Technology Hangzhou 310014 China
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Cabeza L, El-Hammadi MM, Ortiz R, Cayero-Otero MD, Jiménez-López J, Perazzoli G, Martin-Banderas L, Baeyens JM, Melguizo C, Prados J. Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer. BIOIMPACTS : BI 2022; 12:515-531. [PMID: 36644541 PMCID: PMC9809141 DOI: 10.34172/bi.2022.23433] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 02/10/2021] [Accepted: 02/20/2021] [Indexed: 01/18/2023]
Abstract
Introduction: Paclitaxel (PTX) is a cornerstone in the treatment of breast cancer, the most common type of cancer in women. However, this drug has serious limitations, including lack of tissue-specificity, poor water solubility, and the development of drug resistance. The transport of PTX in a polymeric nanoformulation could overcome these limitations. Methods: In this study, PLGA-PTX nanoparticles (NPs) were assayed in breast cancer cell lines, breast cancer stem cells (CSCs) and multicellular tumor spheroids (MTSs) analyzing cell cycle, cell uptake (Nile Red-NR-) and α-tubulin expression. In addition, PLGA-PTX NPs were tested in vivo using C57BL/6 mice, including a biodistribution assay. Results: PTX-PLGA NPs induced a significant decrease in the PTX IC50 of cancer cell lines (1.31 and 3.03-fold reduction in MDA-MB-231 and E0771 cells, respectively) and CSCs. In addition, MTSs treated with PTX-PLGA exhibited a more disorganized surface and significantly higher cell death rates compared to free PTX (27.9% and 16.3% less in MTSs from MCF-7 and E0771, respectively). PTX-PLGA nanoformulation preserved PTX's mechanism of action and increased its cell internalization. Interestingly, PTX-PLGA NPs not only reduced the tumor volume of treated mice but also increased the antineoplastic drug accumulation in their lungs, liver, and spleen. In addition, mice treated with PTX-loaded NPs showed blood parameters similar to the control mice, in contrast with free PTX. Conclusion: These results suggest that our PTX-PLGA NPs could be a suitable strategy for breast cancer therapy, improving antitumor drug efficiency and reducing systemic toxicity without altering its mechanism of action.
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Affiliation(s)
- Laura Cabeza
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
,Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
,Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain
| | - Mazen M. El-Hammadi
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Seville, 41012 Sevilla, Spain
| | - Raul Ortiz
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
,Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
,Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain
| | - Maria D. Cayero-Otero
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Seville, 41012 Sevilla, Spain
| | - Julia Jiménez-López
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
,Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain
| | - Gloria Perazzoli
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
,Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain
| | - Lucia Martin-Banderas
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Seville, 41012 Sevilla, Spain
| | - Jose M. Baeyens
- Department of Pharmacology, Institute of Neuroscience, Biomedical Research Center (CIBM), University of Granada, 18100, Granada, Spain
| | - Consolación Melguizo
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
,Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
,Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain
,Corresponding author: Consolación Melguizo,
| | - Jose Prados
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
,Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
,Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain
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Song J, Wu C, Zhao Y, Yang M, Yao Q, Gao Y. Bioorthogonal Disassembly of Tetrazine Bearing Supramolecular Assemblies Inside Living Cells. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2104772. [PMID: 34843166 DOI: 10.1002/smll.202104772] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 10/18/2021] [Indexed: 06/13/2023]
Abstract
Supramolecular assemblies are an emerging class of nanomaterials for drug delivery systems (DDS), while their unintended retention in the biological milieu remains largely unsolved. To realize the prompt clearance of supramolecular assemblies, the bioorthogonal reaction to disassemble and clear the supramolecular assemblies within living cells is investigated here. A series of tetrazine-capped assembly precursors which can self-assemble into nanofibers and hydrogels upon enzymatic dephosphorylation are designed. Such an enzyme-instructed supramolecular assembly process can perform intracellularly. The time-dependent accumulation of assemblies elicits oxidative stress and induces cellular toxicity. Tetrazine-bearing assemblies react with trans-cyclooctene derivatives, which lead to the disruption of π-π stacking and induce disassembly. In this way, the intracellular self-assemblies disassemble and are deprived of potency. This bioorthogonal disassembly strategy leverages the biosafety aspect in developing nanomaterials for DDSs.
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Affiliation(s)
- Jialei Song
- CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, China
- Sino-Danish Center for Education and Research, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Chengling Wu
- CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, China
| | - Yan Zhao
- CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, China
| | - Min Yang
- CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, China
| | - Qingxin Yao
- CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, China
| | - Yuan Gao
- CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, China
- Sino-Danish Center for Education and Research, University of Chinese Academy of Sciences, Beijing, 100049, China
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Chen Q, Zhang L, Li L, Tan M, Liu W, Liu S, Xie Z, Zhang W, Wang Z, Cao Y, Shang T, Ran H. Cancer cell membrane-coated nanoparticles for bimodal imaging-guided photothermal therapy and docetaxel-enhanced immunotherapy against cancer. J Nanobiotechnology 2021; 19:449. [PMID: 34952587 PMCID: PMC8710014 DOI: 10.1186/s12951-021-01202-x] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 12/10/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Mono-therapeutic modality has limitations in combating metastatic lesions with complications. Although emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. The rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer. RESULTS Poly lactic-co-glycolic acid (PLGA, 50 mg) nanospheres were constructed with photothermal transduction agents (PTAs)-Prussian blue (PB, 2.98 mg) encapsulated in the core and chemotherapeutic docetaxel (DTX, 4.18 mg)/ immune adjuvant-imiquimod (R837, 1.57 mg) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated "M@P-PDR"), which acted as "Nano-targeted cells" to actively accumulate in tumor sites, and were guided/monitored by photoacoustic (PA)/ magnetic resonance (MR) imaging. Upon laser irradiation, photothermal effects were triggered. Combined with DTX, PTT induced in situ tumor eradication. Assisted by the immune adjuvant R837, the maturation rate of DCs increased by 4.34-fold compared with that of the control. In addition, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving the immunosuppressive TME. The proportion of M2-TAMs decreased from 68.57% to 32.80%, and the proportion of M1-TAMs increased from 37.02% to 70.81%. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased from 17.33% (control) to 35.5%. Primary tumors and metastasis were significantly inhibited when treated with "Nano-targeted cells"-based cocktail therapy. CONCLUSION "Nano-targeted cells"-based therapeutic cocktail therapy is a promising approach to promote tumor regression and counter metastasis/recurrence.
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Affiliation(s)
- Qiaoqi Chen
- Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Yuzhong District, Chongqing, 400010, People's Republic of China
| | - Liang Zhang
- Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Yuzhong District, Chongqing, 400010, People's Republic of China.,Department of Ultrasound, The First Affiliated Hospital, Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400042, People's Republic of China
| | - Lin Li
- Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Yuzhong District, Chongqing, 400010, People's Republic of China
| | - Mixiao Tan
- Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Yuzhong District, Chongqing, 400010, People's Republic of China
| | - Weiwei Liu
- Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Yuzhong District, Chongqing, 400010, People's Republic of China
| | - Shuling Liu
- Department of Radiology, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, No. 181 Hanyu Road, Shapingba District, Chongqing, 400030, People's Republic of China
| | - Zhuoyan Xie
- Chongqing General Hospital, University of Chinese Academy of Sciences, No.114 Longshan Road, Yubei District, Chongqing, 401121, People's Republic of China
| | - Wei Zhang
- Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Yuzhong District, Chongqing, 400010, People's Republic of China
| | - Zhigang Wang
- Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Yuzhong District, Chongqing, 400010, People's Republic of China
| | - Yang Cao
- Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Yuzhong District, Chongqing, 400010, People's Republic of China
| | - Tingting Shang
- Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Yuzhong District, Chongqing, 400010, People's Republic of China.
| | - Haitao Ran
- Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Yuzhong District, Chongqing, 400010, People's Republic of China.
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Mudigunda SV, Pemmaraju DB, Paradkar S, Puppala ER, Gawali B, Upadhyayula SM, Vegi Gangamodi N, Rengan AK. Multifunctional Polymeric Nanoparticles for Chemo/Phototheranostics of Retinoblastoma. ACS Biomater Sci Eng 2021; 8:151-160. [PMID: 34933546 DOI: 10.1021/acsbiomaterials.1c01234] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Retinoblastoma (Rb) is the most critical and severe intraocular malignancy occurring in children. The clinical management of retinoblastoma is still challenging due to failure in early detection and control despite the advancements in medical strategies. Early-stage Rb tumors do not occupy major visual fields, so chemo/photothermal therapy (PTT) with biocompatible materials can be a practical approach. Herein, we report multifunctional polymeric nanoparticles (PNPs) entrapped with an FDA-approved anticancer drug, Palbociclib (PCB), and a near-infrared dye, IR820 (IR), as chemo/photothermal agents. These PCB/IR PNPs were evaluated for the combinational effect in the retinoblastoma cell line. Further, the in vivo photoacoustic imaging efficacy and acute toxicity profile of the PNPs were studied in a mice model. The results indicated that the PCB/IR PNPs exhibited a significant cytotoxic effect (86.5 ± 2.3%) in Y79 cell lines than the respective control groups upon exposure to NIR light. Qualitative and quantitative analyses indicated that PCB/IR PNPs with NIR light induction resulted in DNA damage followed by apoptosis. PCB/IR PNPs, when tested in vivo, showed optimal photoacoustic signals. Thus, the combination of PCB and PTT can emerge as a translational modality for retinoblastoma therapy.
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Affiliation(s)
- Sushma Venkata Mudigunda
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Telangana 502285, India
| | - Deepak B Pemmaraju
- Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research Guwahati, Silakatamur, Kamrup, Changsari, Assam 781101, India
| | - Shivangi Paradkar
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Telangana 502285, India
| | - Eswara Rao Puppala
- Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research Guwahati, Silakatamur, Kamrup, Changsari, Assam 781101, India
| | - Basveshwar Gawali
- Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research Guwahati, Silakatamur, Kamrup, Changsari, Assam 781101, India
| | - Suryanarayana Murty Upadhyayula
- Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research Guwahati, Silakatamur, Kamrup, Changsari, Assam 781101, India
| | - Naidu Vegi Gangamodi
- Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research Guwahati, Silakatamur, Kamrup, Changsari, Assam 781101, India
| | - Aravind Kumar Rengan
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Telangana 502285, India
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Jug-PLGA-NPs, a New Form of Juglone with Enhanced Efficiency and Reduced Toxicity on Melanoma. Chin J Integr Med 2021; 28:909-917. [PMID: 34913148 DOI: 10.1007/s11655-021-3461-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/11/2021] [Indexed: 12/24/2022]
Abstract
OBJECTIVE To verrify the anti-tumor efficacy and toxicity between juglone (Jug) and Jug-loaded PLGA nanoparticles (Jug-PLGA-NPs). METHODS Jug-PLGA-NPs were prepared by ultrasonic emulsification. The anti-tumor activity of Jug (2, 3, 4 µg/mL) and Jug-PLGA-NPs (Jug: 2, 3, 4 µg/mL) in vitro was measured by MTT assay and cell apoptosis analysis. The distribution, anti-tumor effect and biological safety in vivo was evaluated on A375 nude mice. RESULTS With the advantage of good penetration and targeting properties, Jug-PLGA-NPs significantly inhibited proliferation and migration of melanoma cells both in vitro and in vivo (P<0.05 or P<0.01) with acceptable biocompatibility. CONCLUSIONS Jug can inhibit the growth of melanoma but is highly toxic. With the advantage of sustained release, tumor targeting, anti-tumor activity and acceptable biological safety, Jug-PLGA-NPs provide a new pharmaceutical form for future application of Jug.
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Zhang J, Zhang Y, Zhao B, Lv M, Chen E, Zhao C, Jiang L, Qian H, Huang D, Zhong Y, Chen W. Cascade-Responsive Hierarchical Nanosystems for Multisite Specific Drug Exposure and Boosted Chemoimmunotherapy. ACS APPLIED MATERIALS & INTERFACES 2021; 13:58319-58328. [PMID: 34855343 DOI: 10.1021/acsami.1c16636] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
The precise delivery of multiple drugs to their distinct destinations plays a significant role in safe and efficient combination therapy; however, it is highly challenging to simultaneously realize the targets and overcome the intricate biological hindrances using an all-in-one nanosystem. Herein, a cascade-responsive hierarchical nanosystem containing checkpoint inhibitor anti-PD-L1 antibody (αPD-L1) and paclitaxel (PTX) is developed for spatially programed delivery of multiple drugs and simultaneously overcoming biological pathway barriers. The hierarchical nanoparticles (MPH-NP@A) are composed of pH-sensitive hyaluronic acid-acetal-PTX prodrugs (HA-ace-PTX(SH)) chaperoned by αPD-L1 and metalloproteinase-9 (MMP-9)-responsive outer shells, which could be fast cleaved to release αPD-L1 in the tumor microenvironment (TME). The released αPD-L1 sequentially synergizes with PTX released in the cytoplasm for boosted chemoimmunotherapy due to direct killing of PTX and intensified immune responses through immunogenic cell death (ICD) as well as suppression of immune escape by blocking the PD-1/PD-L1 axis. The in vitro and in vivo studies demonstrate that MPH-NP@A evokes distinct ICD, enhanced cytotoxic T lymphocytes infiltration, as well as significant tumor inhibition, thus providing a promising therapeutic nano-platform for safe and efficient combination therapy.
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Affiliation(s)
- Junmei Zhang
- Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China
| | - Yuanyuan Zhang
- Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China
| | - Bingbing Zhao
- Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China
| | - Mengtong Lv
- Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China
| | - Enping Chen
- Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China
| | - Changshun Zhao
- Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China
| | - Linyang Jiang
- Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China
| | - Hongliang Qian
- Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China
| | - Dechun Huang
- Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China
- Engineering Research Center for Smart Pharmaceutical Manufacturing Technologies, Ministry of Education, School of Engineering, China Pharmaceutical University, Nanjing 210009, China
| | - Yinan Zhong
- Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China
| | - Wei Chen
- Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China
- Engineering Research Center for Smart Pharmaceutical Manufacturing Technologies, Ministry of Education, School of Engineering, China Pharmaceutical University, Nanjing 210009, China
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Guo K, Xiao N, Liu Y, Wang Z, Tóth J, Gyenis J, Thakur VK, Oyane A, Shubhra QT. Engineering polymer nanoparticles using cell membrane coating technology and their application in cancer treatments: Opportunities and challenges. NANO MATERIALS SCIENCE 2021. [DOI: 10.1016/j.nanoms.2021.12.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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49
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Hamelmann NM, Paats JWD, Paulusse JMJ. Cytosolic Delivery of Single-Chain Polymer Nanoparticles. ACS Macro Lett 2021; 10:1443-1449. [PMID: 35549017 DOI: 10.1021/acsmacrolett.1c00558] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Cytosolic delivery of therapeutic agents is key to improving their efficacy, as the therapeutics are primarily active in specific organelles. Single-chain polymer nanoparticles (SCNPs) are a promising nanocarrier platform in biomedical applications due to their unique size range of 5-20 nm, modularity, and ease of functionalization. However, cytosolic delivery of SCNPs remains challenging. Here, we report the synthesis of active ester-functional SCNPs of approximately 10 nm via intramolecular thiol-Michael addition cross-linking and their functionalization with increasing amounts of tertiary amines 0 to 60 mol % to obtain SCNPs with increasing positive surface charges. No significant cytotoxicity was detected in bEND.3 cells for the SCNPs, except when SCNPs with high amounts of tertiary amines were incubated over prolonged periods of time at high concentrations. Cellular uptake of the SCNPs was analyzed, presenting different uptake behavior depending on the degree of functionalization. Confocal microscopy revealed successful cytosolic delivery of SCNPs with high degrees of functionalization (45%, 60%), while SCNPs with low amounts (0% to 30%) of tertiary amines showed high degrees of colocalization with lysosomes. This work presents a strategy to direct the intracellular location of SCNPs by controlled surface modification to improve intracellular targeting for biomedical applications.
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Affiliation(s)
- Naomi M. Hamelmann
- Department of Molecules and Materials, MESA+ Institute for Nanotechnology and TechMed Institute for Health and Biomedical Technologies, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands
| | - Jan-Willem D. Paats
- Department of Molecules and Materials, MESA+ Institute for Nanotechnology and TechMed Institute for Health and Biomedical Technologies, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands
| | - Jos M. J. Paulusse
- Department of Molecules and Materials, MESA+ Institute for Nanotechnology and TechMed Institute for Health and Biomedical Technologies, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands
- Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen,
P.O. Box 30.001, 9700 RB Groningen, The Netherlands
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Kardani K, Sadat SM, Kardani M, Bolhassani A. The next generation of HCV vaccines: a focus on novel adjuvant development. Expert Rev Vaccines 2021; 20:839-855. [PMID: 34114513 DOI: 10.1080/14760584.2021.1941895] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Considerable efforts have been made to treat and prevent acute and chronic infections caused by the hepatitis C virus (HCV). Current treatments are unable to protect people from reinfection. Hence, there is a need for development of both preventive and therapeutic HCV vaccines. Many vaccine candidates are in development to fight against HCV, but their efficacy has so far proven limited partly due to low immunogenicity. AREAS COVERED We explore development of novel and powerful adjuvants to achieve an effective HCV vaccine. The basis for developing strong adjuvants is to understand the innate immunity pathway, which subsequently stimulates humoral and cellular immune responses. We have also investigated immunogenicity of developed adjuvants that have been used in recent studies available in online databases such as PubMed, PMC, ScienceDirect, Google Scholar, etc. EXPERT OPINION Adjuvants are used as a part of vaccine formulation to boost vaccine immunogenicity and antigen delivery. Several FDA-approved adjuvants are used in licensed human vaccines. Unfortunately, no adjuvant has yet been proven to boost HCV immune responses to the extent needed for an effective vaccine. One of the promising approaches for developing an effective adjuvant is the combination of various adjuvants to trigger several innate immune responses, leading to activation of adaptive immunity.[Figure: see text].
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Affiliation(s)
- Kimia Kardani
- Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran
| | - Seyed Mehdi Sadat
- Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran
| | - Mona Kardani
- Iranian Comprehensive Hemophilia Care Center, Tehran, Iran
| | - Azam Bolhassani
- Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran
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