|
1
|
Sun J, Li HL, Zhou WJ, Ma ZX, Huang XP, Li C. Current status and recent progress of nanomaterials in transcatheter arterial chemoembolization therapy for hepatocellular carcinoma. World J Clin Oncol 2025; 16:104435. [PMID: 40290691 PMCID: PMC12019268 DOI: 10.5306/wjco.v16.i4.104435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 02/06/2025] [Accepted: 03/05/2025] [Indexed: 03/26/2025] Open
Abstract
Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide. Transcatheter arterial chemoembolization has become a common treatment modality for some patients with unresectable advanced HCC. Since the introduction of nanomaterials in 1974, their use in various fields has evolved rapidly. In medical applications, nanomaterials can serve as carriers for the delivery of chemotherapeutic drugs to tumour tissues. Additionally, nanomaterials have potential for in vivo tumour imaging. This article covers the properties and uses of several kinds of nanomaterials, focusing on their use in transcatheter arterial chemoembolization for HCC treatment. This paper also discusses the limitations currently associated with the use of nanomaterials.
Collapse
Affiliation(s)
- Jia Sun
- Department of Hepatobiliary Pancreatic Hernia Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou 510317, Guangdong Province, China
| | - Hai-Liang Li
- Department of Hepatobiliary Pancreatic Hernia Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou 510317, Guangdong Province, China
| | - Wen-Jun Zhou
- Department of Hepatobiliary Pancreatic Hernia Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou 510317, Guangdong Province, China
| | - Zeng-Xin Ma
- Department of Hepatobiliary Pancreatic Hernia Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou 510317, Guangdong Province, China
| | - Xiao-Pei Huang
- Department of Hepatobiliary Pancreatic Hernia Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou 510317, Guangdong Province, China
| | - Cheng Li
- Department of Hepatobiliary Pancreatic Hernia Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou 510317, Guangdong Province, China
| |
Collapse
|
|
2
|
Pandey N, Iyer P, Kadapure TD, Yang J, Nguyen KT, Wadajkar AS. Dual-imaging nanoparticles based on surface-modified magnetic nanoparticles and biodegradable photoluminescent polymers. Front Bioeng Biotechnol 2025; 13:1558817. [PMID: 40276037 PMCID: PMC12018434 DOI: 10.3389/fbioe.2025.1558817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Accepted: 03/26/2025] [Indexed: 04/26/2025] Open
Abstract
Theranostic nanoparticles, which combine diagnostic and therapeutic capabilities, have gained significant interest in disease management. We previously developed dual-imaging enabled cancer-targeting nanoparticles (DICT-NPs) composed of a biodegradable photoluminescent polymer (BPLP) and iron oxide-based superparamagnetic nanoparticles (MNPs). While DICT-NPs demonstrated cytocompatibility, magnetic targeting, and imaging capabilities, their fluorescence was inconsistent due to quenching by the MNP core and inefficient BPLP grafting. To address these limitations, we modified the MNP surface with silane, hydroxyapatite, or silane-coupled azide coatings before conjugating with BPLP. The resulting surface-modified DICT-NPs (mDICT-NPs) ranged in size from 200-350 nm and were cyto-compatible with human dermal fibroblasts and normal human prostate epithelial cells. Surface modifications and BPLP conjugation did not affect the superparamagnetic properties of the nanoparticles but enhanced fluorescence by ∼50% compared to the original DICT-NPs. Hydroxyapatite-modified DICT-NPs exhibited significant improvements, including sustained drug release of Paclitaxel and Docetaxel (71% and 68%, respectively, over 21 days), dose-dependent tumor cell uptake in melanoma, thyroid, and prostate cancer cells (with the highest uptake exceeding 60% at 500 μg/mL), and a reduction in cancer cell viability (less than 50% viability in TT thyroid cancer and KAT-4 cancer cell lines). These advancements represent a significant step in overcoming the fluorescence quenching issues associated with iron oxide-based magneto-fluorescent theranostic nanoparticle platforms, enhancing both their imaging and therapeutic potential in cancer treatment.
Collapse
Affiliation(s)
- Nikhil Pandey
- Department of Bioengineering, The University of Texas at Arlington, Arlington, TX, United States
- Department of Biomedical Engineering, The University of Texas Southwestern Medical Center (UTSW), Dallas, TX, United States
- Department of Neurosurgery, The University of Maryland School of Medicine, Baltimore, MD, United States
- Marlene and Stewart Greenebaum Comprehensive Cancer Center, The University of Maryland School of Medicine, Baltimore, MD, United States
| | - Priyanka Iyer
- Department of Bioengineering, The University of Texas at Arlington, Arlington, TX, United States
- Department of Biomedical Engineering, The University of Texas Southwestern Medical Center (UTSW), Dallas, TX, United States
| | - Tejaswi D. Kadapure
- Department of Bioengineering, The University of Texas at Arlington, Arlington, TX, United States
- Department of Biomedical Engineering, The University of Texas Southwestern Medical Center (UTSW), Dallas, TX, United States
| | - Jian Yang
- Department of Materials Science and Engineering, Westlake University, Hangzhou, Zhejiang, China
- Research Centre for Industries of the Future, Westlake University, Hangzhou, Zhejiang, China
| | - Kytai T. Nguyen
- Department of Bioengineering, The University of Texas at Arlington, Arlington, TX, United States
- Department of Biomedical Engineering, The University of Texas Southwestern Medical Center (UTSW), Dallas, TX, United States
| | - Aniket S. Wadajkar
- Department of Bioengineering, The University of Texas at Arlington, Arlington, TX, United States
- Department of Biomedical Engineering, The University of Texas Southwestern Medical Center (UTSW), Dallas, TX, United States
| |
Collapse
|
|
3
|
Bhattacharjee S, Aswal VK, Seth D. Unraveling the Role of Polyoxometalates-Based Superchaotropes on the Photophysics of Organic Molecules and Modulation of Water Dynamics in a Hydrophilic Block Copolymer Solution. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2025; 41:2331-2346. [PMID: 39842039 DOI: 10.1021/acs.langmuir.4c03990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/24/2025]
Abstract
Polyoxometalates (POMs) are composed of nanometric metal-oxide anions and have rich solution chemistry. In this class, Keggin POMs have been identified as the most influential inorganic additives for aqueous nonionic soft matter systems. POMs being at the borderline of classical ions and charged colloids possess fascinating solution properties; the present work aims to delve deeper into the interactions between nanoions and nonionic soft matters from a spectroscopic point of view. Our studies reveal that although of the same structural makeup, silicotungstic acid hydrate (SiW) and phosphotungstic acid hydrate (PW) affect the photophysics of Coumarin-480 (C-480) in poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) ((PEO)76-(PPO)30-(PEO)76, F-68) copolymeric media in a dissimilar manner. From time-resolved studies, we find a preference for SiW toward the intramolecular charge transfer state of C-480, whereas PW favors the locally emissive state of the probe. Further, from rotational relaxation studies, it appears that SiW renders a rigid environment around the probe molecule, while PW relaxes the copolymeric environment. Finally, the dynamic quenching mechanism of the added nanoions was unraveled, which showed a straightforward Förster mechanism for SiW but a short-range interaction was operative for PW. From Fourier transform infrared and 1H NMR, it can be concluded that both the nanoions interacted with the PPO moiety of the copolymer; yet, their contrasting effect on the photophysics has been rationalized as a consequence of charge density on the ions.
Collapse
Affiliation(s)
- Sanyukta Bhattacharjee
- Department of Chemistry, Indian Institute of Technology Patna, Patna 801103, Bihar, India
| | - Vinod K Aswal
- Solid State Physics Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India
| | - Debabrata Seth
- Department of Chemistry, Indian Institute of Technology Patna, Patna 801103, Bihar, India
| |
Collapse
|
|
4
|
Yin M, Zhang X, Zhang T, Bao Z, He Z. Folic Acid-Targeted Mixed Pluronic Micelles for Delivery of Triptolide. Polymers (Basel) 2024; 16:3485. [PMID: 39771337 PMCID: PMC11677570 DOI: 10.3390/polym16243485] [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: 10/21/2024] [Revised: 12/11/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025] Open
Abstract
The present study aimed to explore an ideal delivery system for triptolide (TPL) by utilizing the thin-film hydration method to prepare drug-loaded, folate-modified mixed pluronic micelles (FA-F-127/F-68-TPL). Scanning electron microscopy and atomic force microscopy showed that the drug-loaded micelles had a spherical shape with a small particle size, with an average of 30.7 nm. Cell viability experiments showed that FA-F-127/F-68-TPL significantly reduced HepG2 cell viability, exhibiting strong cytotoxicity. Its cytotoxicity was markedly enhanced compared with bare TPL. Nile red (Nr) was used as a model drug to prepare FA-F-127/F-68-Nr to further validate its tumor-targeting and cellular uptake capability. After coincubation with HepG2 cells, a multifunctional microplate reader showed that intracellular fluorescence intensity significantly increased, indicating that FA-F-127/F-68-Nr could more effectively enter the cells. A nude mouse model of subcutaneous hepatocellular carcinoma was constructed. Following tail vein injection of FA-F-127/F-68-Nr, the fluorescence imaging system showed that FA-F127/F-68-Nr could significantly target tumor tissue, and even if entering the small-sized tumor was challenging, it could be excreted through urine. Nude mice with subcutaneous hepatocellular carcinoma were treated with tail vein injections of FA-F-127/F-68-TPL (45 µg/kg) every other day for 21 days. The results showed that the growth of the transplanted tumors was significantly slowed, with no significant difference compared with bare TPL. In summary, the FA-F-127/F-68-TPL exhibits the advantages of low cost, excellent biological properties, active/passive targeting capabilities, notable cytotoxicity against liver cancer cells, and significant inhibition of transplanted hepatocellular carcinoma growth. Significantly, the FA-F-127/F-68-TPL, despite challenges in targeting tumors with an insignificant EPR effect, can be efficiently excreted via the kidneys, thereby preventing the release of the drug during prolonged circulation and potential damage to normal tissues. Therefore, FA-F-127/F-68-TPL represents a promising antitumor drug delivery system.
Collapse
Affiliation(s)
- Meizhen Yin
- Medical College, Inner Mongolia Minzu University, Tongliao 028043, China
| | | | | | | | | |
Collapse
|
|
5
|
Mohammadi Zonouz A, Taghavi S, Nekooei S, Abnous K, Taghdisi SM, Ramezani M, Alibolandi M. Synthesis of targeted doxorubicin-loaded gold nanorod -mesoporous manganese dioxide core-shell nanostructure for ferroptosis, chemo-photothermal therapy in vitro and in vivo. Int J Pharm 2024; 665:124725. [PMID: 39293581 DOI: 10.1016/j.ijpharm.2024.124725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 09/14/2024] [Accepted: 09/14/2024] [Indexed: 09/20/2024]
Abstract
In the current study, a core-shell inorganic nanostructure comprising a gold nanorod core and -mesoporous manganese dioxide shell was synthesized. Then, the mesoporous manganese dioxide shell was loaded with doxorubicin (DOX) and then coated with pluronic F127 and pluronic F127-folic acid conjugate (1.5:1 wt ratio of pluronic F127: pluronic F127-folic acid conjugate) to prepare targeted final platform. In this design, mesoporous manganese dioxide acted as a reservoir for DOX loading, anti-hypoxia, and MRI contrast agent, while the gold nanorod core acted as a photothermal and CT scan imaging agent. DOX was encapsulated in the mesoporous manganese dioxide shell with a loading capacity and loading efficiency of 19.8 % ± 0.2 and 99.0 % ± 0.9, respectively. The in vitro release experiment showed the impact of glutathione (GSH), mildly acidic pH, and laser irradiating toward accelerated stimuli-responsive DOX release. The ·OH production of the prepared platform was verified by methylene blue (MB) decomposition reaction. Furthermore, thermal imaging exhibited the ability of the prepared platform to convert the NIR irradiation to heat. In vitro cytotoxicity tests on the folate receptor-positive 4 T1 cell line revealed the remarkable cytotoxicity of the targeted formulation compared to the nontargeted formulation (statistically significant). The MTT experiment demonstrated that exposure to laser 808 irradiation enhanced cytotoxicity of the targeted formulation (p < 0.0001). The production of ROS in 4 T1 cells following treatment with the targeted formulation was demonstrated by the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. Furthermore, in vivo investigations by implementing subcutaneous 4 T1 tumorized female BABL/c mice indicated that the prepared platform was an effective system in suppressing tumor growth by combining chemotherapy with PTT (photothermal therapy). Additionally, simultanous PTT and anti-hypoxic activity of this system showed potent tumor growth suppression impact. The percent of tumor size reduction in mice treated with FA-F127-DOX@Au-MnO2 + 808 nm laser compared to the control group was 99.7 %. The results of the biodistribution investigation showed tumor accumulation and modified pharmacokinetics of the targeted system. Lastly, 6 and 24 h post-intravenous injection, CT-scan and MR imagings capability of the prepared platform was verified in preclinical stage. The prepared multipurpose system introduces great opportunity to provide multiple treatment strategy along with multimodal imaging capability in a single platform for breast cancer treatment.
Collapse
Affiliation(s)
- Aidin Mohammadi Zonouz
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sahar Taghavi
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sirous Nekooei
- Department of Radiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Khalil Abnous
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medicinal Chemistry Department, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Mohammad Taghdisi
- Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Ramezani
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Mona Alibolandi
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
| |
Collapse
|
|
6
|
Wei J, Xu H, Sun Y, Liu Y, Yan R, Chen Y, Zhang Z. Magnetite Nanoparticle Assemblies and Their Biological Applications: A Review. Molecules 2024; 29:4160. [PMID: 39275008 PMCID: PMC11397167 DOI: 10.3390/molecules29174160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 08/25/2024] [Accepted: 08/29/2024] [Indexed: 09/16/2024] Open
Abstract
Magnetite nanoparticles (Fe3O4 NPs) have garnered significant attention over the past twenty years, primarily due to their superparamagnetic properties. These properties allow the NPs to respond to external magnetic fields, making them particularly useful in various technological applications. One of the most fascinating aspects of Fe3O4 NPs is their ability to self-assemble into complex structures. Research over this period has focused heavily on how these nanoparticles can be organized into a variety of superstructures, classified by their dimensionality-namely one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) configurations. Despite a wealth of studies, the literature lacks a systematic review that synthesizes these findings. This review aims to fill that gap by providing a thorough overview of the recent progress made in the fabrication and organization of Fe3O4 NP assemblies via a bottom-up self-assembly approach. This methodology enables the controlled construction of assemblies at the nanoscale, which can lead to distinctive functionalities compared to their individual counterparts. Furthermore, the review explores the diverse applications stemming from these nanoparticle assemblies, particularly emphasizing their contributions to important areas such as imaging, drug delivery, and the diagnosis and treatment of cancer.
Collapse
Affiliation(s)
- Jinjian Wei
- College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, China
| | - Hong Xu
- College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, China
| | - Yating Sun
- College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, China
| | - Yingchun Liu
- Jinan Guoke Medical Technology Development Co., Ltd., Jinan 250000, China
| | - Ran Yan
- Jinan Petrochemical Design Institute, Jinan 250100, China
| | - Yuqin Chen
- College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, China
| | - Zhide Zhang
- College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, China
| |
Collapse
|
|
7
|
Yin Q, Gao X, Zhang H, Zhang Z, Yu X, He J, Shi G, Hao L. Fe 3O 4-Cy5.5-trastuzumab magnetic nanoparticles for magnetic resonance/near-infrared imaging targeting HER2 in breast cancer. Biomed Mater 2024; 19:035034. [PMID: 38626777 DOI: 10.1088/1748-605x/ad3f61] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 04/16/2024] [Indexed: 04/26/2024]
Abstract
This study developed a probe Fe3O4-Cy5.5-trastuzumab with fluorescence and magnetic resonance imaging functions that can target breast cancer with high HER2 expression, aiming to provide a new theoretical method for the diagnosis of early breast cancer. Fe3O4-Cy5.5-trastuzumab nanoparticles were combined with Fe3O4for T2imaging and Cy5.5 for near-infrared imaging, and coupled with trastuzumab for HER2 targeting. We characterized the nanoparticles used transmission electron microscopy, hydration particle size, Zeta potential, UV and Fourier transform infrared spectroscopy, and examined its magnetism, fluorescence, and relaxation rate related properties. CCK-8 and blood biochemistry analysis evaluated the biosafety and stability of the nanoparticles, and validated the targeting ability of Fe3O4-Cy5.5 trastuzumab nanoparticles throughin vitroandin vivocell and animal experiments. Characterization results showed the successful synthesis of Fe3O4-Cy5.5-trastuzumab nanoparticles with a diameter of 93.72 ± 6.34 nm. The nanoparticles showed a T2relaxation rate 42.29 mM-1s-1, magnetic saturation strength of 27.58 emg g-1. Laser confocal and flow cytometry uptake assay showed that the nanoparticles could effectively target HER2 expressed by breast cancer cells. As indicated byin vitroandin vivostudies, Fe3O4-Cy5.5-trastuzumab were specifically taken up and effectively aggregated to tumour regions with prominent NIRF/MR imaging properties. CCK-8, blood biochemical analysis and histological results suggested Fe3O4-Cy5.5-trastuzumab that exhibited low toxicity to major organs and goodin vivobiocompatibility. The prepared Fe3O4-Cy5.5-trastuzumab exhibited excellent targeting, NIRF/MR imaging performance. It is expected to serve as a safe and effective diagnostic method that lays a theoretical basis for the effective diagnosis of early breast cancer. This study successfully prepared a kind of nanoparticles with near-infrared fluorescence imaging and T2imaging properties, which is expected to serve as a new theory and strategy for early detection of breast cancer.
Collapse
Affiliation(s)
- Qiangqiang Yin
- Department of Molecular Imaging, School of Medical Technology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, People's Republic of China
| | - Xiaolong Gao
- Department of Imaging, Fu Jin Hospital of Traditional Chinese Medicine, Jiamusi, Heilongjiang 156100, People's Republic of China
| | - Hao Zhang
- Department of Molecular Imaging, School of Medical Technology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, People's Republic of China
| | - Zhichen Zhang
- Department of Molecular Imaging, School of Medical Technology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, People's Republic of China
| | - Xiaoyang Yu
- Department of Molecular Imaging, School of Medical Technology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, People's Republic of China
| | - Jialong He
- Department of Molecular Imaging, School of Medical Technology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, People's Republic of China
| | - Guangyue Shi
- Department of Molecular Imaging, School of Medical Technology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, People's Republic of China
| | - Liguo Hao
- Department of Molecular Imaging, School of Medical Technology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, People's Republic of China
| |
Collapse
|
|
8
|
Chen CY, Chen CY. Targeted and Oxygen-Enriched Nanoplatform for Enhanced Photodynamic Therapy: In Vitro 2D Cell and 3D Spheroid Model Evaluation. Macromol Biosci 2023; 23:e2300196. [PMID: 37565670 DOI: 10.1002/mabi.202300196] [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: 05/06/2023] [Revised: 07/05/2023] [Indexed: 08/12/2023]
Abstract
Hypoxic microenvironment and limited penetration of photosensitizers within solid tumors are two crucial factors that restrict photodynamic therapy (PDT) efficacy. Herein, a new fluorinated mixed micelle (M60@PFC-Ce6) is developed as a tumor-penetrating and oxygen-enriching nanoplatform, which consists of chlorin e6 (Ce6) and perfluorocarbons (PFCs) co-loaded into fluorinated micelles to relieve hypoxia conditions as well as folate as targeting ligand that facilitates the selective biodistribution within tumor solids. The incorporation of fluorinated copolymers into mixed micelles exhibits not only a great increase in the oxygen-loading capacity, but also improves the stability of liquid PFCs emulsion within micelles without leakage. M60@PFC-Ce6 shows excellent oxygen delivery capability, good intracellular reactive oxygen species (ROS) generation, and superior phototoxicity in vitro for both 2D monolayer of cells and 3D multicellular spheroid model. These results indicate the enriched oxygen delivery and increased cellular uptake resulting from folate-targeted ability to enhance ROS production and PDT efficacy. The penetration study of M60@PFC-Ce6 into a 3D spheroid confirms that small micellar size and folate-conjugation are beneficial for micelles to penetrate and accumulate within spheroids. Thus, a new nanoplatform with enriched oxygen-carrying amounts, better drug penetration, and stable micellar properties that relieve tumor hypoxia and improve PDT efficacy is provided.
Collapse
Affiliation(s)
- Chieh-Yu Chen
- Department of Chemical Engineering, National Chung Cheng University, Chia-Yi County, 62102, Taiwan
| | - Ching-Yi Chen
- Department of Chemical Engineering, National Chung Cheng University, Chia-Yi County, 62102, Taiwan
| |
Collapse
|
|
9
|
George S, Srinivasan A, Tulimilli SV, Madhunapantula SV, Palantavida S. Folate targeting self-limiting hyperthermic nanoparticles for controlled photothermal therapy. J Mater Chem B 2023. [PMID: 37379103 DOI: 10.1039/d3tb00899a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/29/2023]
Abstract
Photothermal therapy utilizes photothermal agents and the use of nanoparticle agents is deemed advantageous for multiple reasons. Common nano-photothermal agents normally have high conversion efficiencies and heating rates, but bulk temperature measurement methods do not adequately represent the nanoscale temperatures of these nanoheaters. Herein, we report on the fabrication of self-limiting hyperthermic nanoparticles that can simultaneously photoinduce hyperthermia and report back temperature ratiometrically. The synthesized nanoparticles utilize a plasmonic core to achieve the photoinduced hyperthermic property and fluorescent FRET pairs entrapped in a silica shell to impart the ratiometric temperature sensing ability. The studies demonstrate the photoinduced hyperthermia with simultaneous temperature measurement using these particles and show that the particles can achieve a conversion efficiency of 19.5% despite the shell architecture. These folate-functionalized self-limiting photothermal agents are also used to demonstrate targeted photoinduced hyperthermia in a HeLa cell model.
Collapse
Affiliation(s)
- Sharon George
- Centre for Nano and Material Sciences, Jain (Deemed-to-be University), Jain Global Campus, Kanakapura, Bangalore, Karnataka, 562112, India.
| | - Asha Srinivasan
- Division of Nanoscience and Technology, School of Life Sciences, JSS Academy of Higher Education & Research, Mysuru, Karnataka, 570015, India
| | - SubbaRao V Tulimilli
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru, Karnataka, 570015, India
| | - SubbaRao V Madhunapantula
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru, Karnataka, 570015, India
| | - Shajesh Palantavida
- Centre for Nano and Material Sciences, Jain (Deemed-to-be University), Jain Global Campus, Kanakapura, Bangalore, Karnataka, 562112, India.
| |
Collapse
|
|
10
|
de Freitas CF, de Araújo Santos J, Pellosi DS, Caetano W, Batistela VR, Muniz EC. Recent advances of Pluronic-based copolymers functionalization in biomedical applications. BIOMATERIALS ADVANCES 2023; 151:213484. [PMID: 37276691 DOI: 10.1016/j.bioadv.2023.213484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 05/22/2023] [Accepted: 05/25/2023] [Indexed: 06/07/2023]
Abstract
The design of polymeric biocompatible nanomaterials for biological and medical applications has received special attention in recent years. Among different polymers, the triblock type copolymers (EO)x(PO)y(EO)x or Pluronics® stand out due its favorable characteristics such as biocompatibility, low tissue adhesion, thermosensitivity, and structural capacity to produce different types of macro and nanostructures, e.g. micelles, vesicles, nanocapsules, nanospheres, and hydrogels. However, Pluronic itself is not the "magic bullet" and its functionalization via chemical synthesis following biologically oriented design rules is usually required aiming to improve its properties. Therefore, this paper presents some of the main publications on new methodologies for synthetic modifications and applications of Pluronic-based nanoconstructs in the biomedical field in the last 15 years. In general, the polymer modifications aim to improve physical-chemical properties related to the micellization process or physical entrapment of drug cargo, responsive stimuli, active targeting, thermosensitivity, gelling ability, and hydrogel formation. Among these applications, it can be highlighted the treatment of malignant neoplasms, infectious diseases, wound healing, cellular regeneration, and tissue engineering. Functionalized Pluronic has also been used for various purposes, including medical diagnosis, medical imaging, and even miniaturization, such as the creation of lab-on-a-chip devices. In this context, this review discusses the main scientific contributions to the designing, optimization, and improvement of covalently functionalized Pluronics aiming at new strategies focused on the multiple areas of the biomedical field.
Collapse
Affiliation(s)
- Camila Fabiano de Freitas
- Department of Chemistry, Federal University of Santa Catarina - UFSC, Eng. Agronômico Andrei Cristian Ferreira, s/n, Trindade, 88040-900 Florianópolis, Santa Catarina, Brazil.
| | - Jailson de Araújo Santos
- PhD Program in Materials Science and Engineering, Federal University of Piauí, Campus Petrônio Portela, Ininga, Teresina CEP 64049-550, Piauí, Brazil
| | - Diogo Silva Pellosi
- Laboratory of Hybrid Materials, Department of Chemistry, Federal University of São Paulo, Diadema, Brazil
| | - Wilker Caetano
- Department of Chemistry, State University of Maringá, 5790 Colombo Avenue, 87020-900 Maringá, Paraná, Brazil
| | - Vagner Roberto Batistela
- Department of Pharmacology and Therapeutics, State University of Maringá, 5790 Colombo Avenue, 87020-900 Maringá, Paraná, Brazil
| | - Edvani Curti Muniz
- Department of Chemistry, State University of Maringá, 5790 Colombo Avenue, 87020-900 Maringá, Paraná, Brazil; Department of Chemistry, Federal University of Piauí, Campus Petronio Portella, Ininga, Teresina CEP 64049-550, Piauí, Brazil.
| |
Collapse
|
|
11
|
Carrera Espinoza MJ, Lin KS, Weng MT, Kunene SC, Lin YS, Wu CM. Synthesis and Characterization of Supermagnetic Nanocomposites Coated with Pluronic F127 as a Contrast Agent for Biomedical Applications. Pharmaceutics 2023; 15:740. [PMID: 36986601 PMCID: PMC10053918 DOI: 10.3390/pharmaceutics15030740] [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: 01/05/2023] [Revised: 02/09/2023] [Accepted: 02/21/2023] [Indexed: 02/25/2023] Open
Abstract
Nanomedicine has garnered significant interest owing to advances in drug delivery, effectively demonstrated in the treatment of certain diseases. Here, smart supermagnetic nanocomposites based on iron oxide nanoparticles (MNPs) coated with Pluronic F127 (F127) were developed for the delivery of doxorubicin (DOX) to tumor tissues. The XRD patterns for all samples revealed peaks consistent with Fe3O4, as shown by their indices (220), (311), (400), (422), (511), and (440), demonstrating that the structure of Fe3O4 did not change after the coating process. After loading with DOX, the as-prepared smart nanocomposites demonstrated drug-loading efficiency and drug-loading capacity percentages of 45 ± 0.10 and 17 ± 0.58% for MNP-F127-2-DOX and 65 ± 0.12 and 13 ± 0.79% for MNP-F127-3-DOX, respectively. Moreover, a better DOX release rate was observed under acidic conditions, which may be credited to the pH sensitivity of the polymer. In vitro analysis demonstrated the survival rate of approximately 90% in HepG2 cells treated with PBS and MNP-F127-3 nanocomposites. Furthermore, after treatment with MNP-F127-3-DOX, the survival rate decreased, confirming cellular inhibition. Hence, the synthesized smart nanocomposites showed great promise for drug delivery in liver cancer treatment, overcoming the limitations of traditional therapies.
Collapse
Affiliation(s)
- Maria Janina Carrera Espinoza
- Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung–Li District, Taoyuan City 320, Taiwan
| | - Kuen-Song Lin
- Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung–Li District, Taoyuan City 320, Taiwan
| | - Meng-Tzu Weng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
- Department of Medical Research, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu 302, Taiwan
| | - Sikhumbuzo Charles Kunene
- Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung–Li District, Taoyuan City 320, Taiwan
| | - You-Sheng Lin
- Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung–Li District, Taoyuan City 320, Taiwan
| | - Chun-Ming Wu
- National Synchrotron Radiation Research Center, Hsinchu Science Park, Hsinchu 300, Taiwan
| |
Collapse
|
|
12
|
De A, Roychowdhury P, Bhuyan NR, Ko YT, Singh SK, Dua K, Kuppusamy G. Folic Acid Functionalized Diallyl Trisulfide-Solid Lipid Nanoparticles for Targeting Triple Negative Breast Cancer. Molecules 2023; 28:molecules28031393. [PMID: 36771058 PMCID: PMC9921651 DOI: 10.3390/molecules28031393] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 01/27/2023] [Accepted: 01/29/2023] [Indexed: 02/05/2023] Open
Abstract
DATS (diallyl trisulfide), an anti-oxidant and cytotoxic chemical derived from the plant garlic, has been found to have potential therapeutic activity against triple-negative breast cancer (TNBC). Its hydrophobicity, short half-life, lack of target selectivity, and limited bioavailability at the tumor site limit its efficacy in treating TNBC. Overexpression of the Folate receptor on the surface of TNBC is a well-known target receptor for overcoming off-targeting, and lipid nanoparticles solve the limitations of limited bioavailability and short half-life. In order to overcome these constraints, we developed folic acid (FA)-conjugated DATS-SLNs in this research. The design of experiment (DoE) method was employed to optimize the FA-DATS-SLNs' nanoformulation, which resulted in a particle size of 168.2 ± 3.78 nm and a DATS entrapment of 71.91 ± 6.27%. The similarity index between MCF-7 and MDA-MB-231 cell lines demonstrates that FA-DATS-SLNs are more therapeutically efficacious in the treatment of aggravating TNBC. Higher cellular internalization and efficient Bcl2 protein downregulation support the hypothesis that functionalization of the FA on the surface of DATS-SLNs improves anticancer efficacy when compared with DATS and DATS-SLNs. FA-functionalized DATS-SLNs have demonstrated to be a promising therapeutic strategy for TNBC management.
Collapse
Affiliation(s)
- Anindita De
- College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 21936, Republic of Korea
- Correspondence: (A.D.); (G.K.); Tel.: +82-1098218750 (A.D.); +91-9443089812 (G.K.)
| | - Parikshit Roychowdhury
- Department of Pharmaceutical Chemistry, Himalayan Pharmacy Institute, Majitar 737136, East Sikkim, India
| | - Nihar Ranjan Bhuyan
- Department of Pharmaceutical Chemistry, Himalayan Pharmacy Institute, Majitar 737136, East Sikkim, India
| | - Young Tag Ko
- College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 21936, Republic of Korea
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India
| | - Kamal Dua
- Faculty of Health, Australian Research Centre in Complementary & Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW 2007, Australia
| | - Gowthamarajan Kuppusamy
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty 643001, Tamil Nadu, India
- Correspondence: (A.D.); (G.K.); Tel.: +82-1098218750 (A.D.); +91-9443089812 (G.K.)
| |
Collapse
|
|
13
|
de Morais FAP, De Oliveira ACV, Balbinot RB, Lazarin-Bidóia D, Ueda-Nakamura T, de Oliveira Silva S, da Silva Souza Campanholi K, da Silva Junior RC, Gonçalves RS, Caetano W, Nakamura CV. Multifunctional Nanoparticles as High-Efficient Targeted Hypericin System for Theranostic Melanoma. Polymers (Basel) 2022; 15:polym15010179. [PMID: 36616529 PMCID: PMC9824163 DOI: 10.3390/polym15010179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 12/20/2022] [Accepted: 12/23/2022] [Indexed: 12/31/2022] Open
Abstract
Biotin, spermine, and folic acid were covalently linked to the F127 copolymer to obtain a new drug delivery system designed for HY-loaded PDT treatment against B16F10 cells. Chemical structures and binders quantification were performed by spectroscopy and spectrophotometric techniques (1NMR, HABA/Avidin reagent, fluorescamine assay). Critical micelle concentration, critical micelle temperature, size, polydispersity, and zeta potential indicate the hydrophobicity of the binders can influence the physicochemical parameters. Spermine-modified micelles showed fewer changes in their physical and chemical parameters than the F127 micelles without modification. Furthermore, zeta potential measurements suggest an increase in the physical stability of these carrier systems. The phototherapeutic potential was demonstrated using hypericin-loaded formulation against B16F10 cells, which shows that the combination of the binders on F127 copolymer micelles enhances the photosensitizer uptake and potentializes the photodynamic activity.
Collapse
Affiliation(s)
- Flávia Amanda Pedroso de Morais
- Technological Innovation Laboratory in the Pharmaceuticals and Cosmetics Development, State University of Maringá, Maringá 87020-900, PR, Brazil
- Department of Chemistry, State University of Maringá, Maringá 87020-900, PR, Brazil
- Correspondence: (F.A.P.d.M.); (C.V.N.); Tel.: +55-(44)-3011-3680 (F.A.P.d.M. & C.V.N.)
| | | | - Rodolfo Bento Balbinot
- Technological Innovation Laboratory in the Pharmaceuticals and Cosmetics Development, State University of Maringá, Maringá 87020-900, PR, Brazil
| | - Danielle Lazarin-Bidóia
- Technological Innovation Laboratory in the Pharmaceuticals and Cosmetics Development, State University of Maringá, Maringá 87020-900, PR, Brazil
| | - Tânia Ueda-Nakamura
- Technological Innovation Laboratory in the Pharmaceuticals and Cosmetics Development, State University of Maringá, Maringá 87020-900, PR, Brazil
| | - Sueli de Oliveira Silva
- Technological Innovation Laboratory in the Pharmaceuticals and Cosmetics Development, State University of Maringá, Maringá 87020-900, PR, Brazil
| | | | | | - Renato Sonchini Gonçalves
- Laboratory of Chemistry of Natural Products, Department of Chemistry, Center for Exact Sciences and Technology, Federal University of Maranhão, São Luís 65080-805, MA, Brazil
| | - Wilker Caetano
- Department of Chemistry, State University of Maringá, Maringá 87020-900, PR, Brazil
| | - Celso Vataru Nakamura
- Technological Innovation Laboratory in the Pharmaceuticals and Cosmetics Development, State University of Maringá, Maringá 87020-900, PR, Brazil
- Correspondence: (F.A.P.d.M.); (C.V.N.); Tel.: +55-(44)-3011-3680 (F.A.P.d.M. & C.V.N.)
| |
Collapse
|
|
14
|
Seyedi SMR, Asoodeh A, Darroudi M. The human immune cell simulated anti-breast cancer nanorobot: the efficient, traceable, and dirigible anticancer bio-bot. Cancer Nanotechnol 2022; 13:44. [DOI: 10.1186/s12645-022-00150-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 12/01/2022] [Indexed: 12/15/2022] Open
Abstract
Abstract
Background
Various types of cancer therapy strategies have been investigated and successfully applied so far. There are a few modern strategies for improving drug selectivity and biocompatibility, such as nanoparticle-based drug delivery systems. Herein, we designed the traceable enzyme-conjugated magnetic nanoparticles to target human breast cancer cells by simulating the innate immune cell’s respiratory explosion response.
Methods
The human immune cell simulated anti-breast cancer-nanorobot (hisABC-NB) was produced by conjugating the mouse-derived iNOS and human-originated MPO enzymes on the folate-linked chitosan-coated Fe3O4 nanoparticles. The synthesized nanoparticles were functionalized with folic acid as the breast cancer cell detector. Then, the hisABC-NB’s stability and structural properties were characterized by studying Zeta-potential, XRD, FTIR, VSM, FESEM, and DLS analysis. Next, the selectivity and anti-tumor activity of the hisABC-NB were comparatively analyzed on both normal (MCF-10) and cancerous (MCF-7) human breast cells by analyzing the cells’ survival, apoptotic gene expression profile (P53, BAX, BCL2), and flow cytometry data. Finally, the hisABC-NB’s traceability was detected by T2-weighted MRI imaging on the balb-c breast tumor models.
Results
The hisABC-NB significantly reduced the MCF-7 human breast cancer cells by inducing apoptosis response and arresting the cell cycle at the G2/M phase compared with the normal cell type (MCF-10). Moreover, the hisABC-NB exhibited a proper MRI contrast at the tumor region of treated mice compared with the non-treated type, which approved their appropriate MRI-mediated traceability.
Conclusion
The hisABC-NB’s traceability, dirigibility, and selective cytotoxicity were approved, which are the three main required factors for an efficient anticancer compound. Therefore, it has the potential to be used as an intelligent safe anticancer agent for human breast cancer treatment. However, several in vitro and in vivo studies are required to clarify its selectivity, stability, and safety.
Collapse
|
|
15
|
de Oliveira ACV, de Morais FAP, Campanholi KDSS, Bidóia DL, Balbinot RB, Nakamura CV, Caetano W, Hioka N, Monteiro ODS, da Rocha CQ, Gonçalves RS. Melanoma-targeted photodynamic therapy based on hypericin-loaded multifunctional P123-spermine/folate micelles. Photodiagnosis Photodyn Ther 2022; 40:103103. [PMID: 36057363 DOI: 10.1016/j.pdpdt.2022.103103] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 08/18/2022] [Accepted: 08/30/2022] [Indexed: 12/14/2022]
Abstract
Multifunctional P123 micelle linked covalently with spermine (SM) and folic acid (FA) was developed as a drug delivery system of hypericin (HYP). The chemical structures of the modified copolymers were confirmed by spectroscopy and spectrophotometric techniques (UV-vis, FTIR, and 1H NMR). The copolymeric micelles loading HYP were prepared by solid dispersion and characterized by UV-vis, fluorescence, dynamic light scattering (DLS), ζ potential, and transmission electron microscopy (TEM). The results provided a good level of stability for HYP-loaded P123-SM, P123-FA, and P123-SM/P123-FA in the aqueous medium. The morphology analysis showed that all copolymeric micelles are spherical. Well-defined regions of different contrast allow us to infer that SM and FA were localized on the surface of micelles, and the HYP molecules are located in the core region of micelles. The uptake potential of multifunctional P123 micelle was accessed by exposing the micellar systems loading HYP to two cell lines, B16-F10 and HaCaT. HYP-loaded P123 micelles reveal a low selectivity for melanoma cells, showing significant photodamage for HaCat cells. However, the exposition of B16-F10 cells to Hyp-loaded SM- and FA-functionalized P123 micelles under light irradiation revealed the lowest CC50 values. The interpretation of these results suggested that the combination of SM and FA on P123 micelles is the main factor in enhancing the HYP uptake by melanoma cells, consequently leading to its photoinactivation.
Collapse
Affiliation(s)
| | | | | | - Danielle Lazarin Bidóia
- Department of Physics, State University of Maringá, 5790 Colombo Ave., 87020-900 Maringá, PR, Brazil
| | - Rodolfo Bento Balbinot
- Department of Physics, State University of Maringá, 5790 Colombo Ave., 87020-900 Maringá, PR, Brazil
| | - Celso Vataru Nakamura
- Department of Physics, State University of Maringá, 5790 Colombo Ave., 87020-900 Maringá, PR, Brazil
| | - Wilker Caetano
- Department of Chemistry, State University of Maringá, 5790 Colombo Ave., 87020-900 Maringá, PR, Brazil
| | - Noboru Hioka
- Department of Chemistry, State University of Maringá, 5790 Colombo Ave., 87020-900 Maringá, PR, Brazil
| | - Odair Dos Santos Monteiro
- Laboratory of Chemistry of Natural Products, Department of Chemistry, Center for Exact Sciences and Technology, Federal University of Maranhão, São Luís, MA, Brazil
| | - Cláudia Quintino da Rocha
- Laboratory of Chemistry of Natural Products, Department of Chemistry, Center for Exact Sciences and Technology, Federal University of Maranhão, São Luís, MA, Brazil
| | - Renato Sonchini Gonçalves
- Laboratory of Chemistry of Natural Products, Department of Chemistry, Center for Exact Sciences and Technology, Federal University of Maranhão, São Luís, MA, Brazil.
| |
Collapse
|
|
16
|
Espinoza MJC, Lin KS, Weng MT, Kunene SC, Liu SY, Lin YS. In vivo and in vitro studies of magnetic silica nanocomposites decorated with Pluronic F127 for controlled drug delivery system. J IND ENG CHEM 2022. [DOI: 10.1016/j.jiec.2022.08.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
|
|
17
|
Bhendale M, Srivastava A, Singh JK. Insights into the Phase Diagram of Pluronic L64 Using Coarse-Grained Molecular Dynamics Simulations. J Phys Chem B 2022; 126:4731-4744. [PMID: 35708274 DOI: 10.1021/acs.jpcb.2c02429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
We investigate the concentration-dependent phase diagram of pluronic L64 in aqueous media at 300 and 320 K using coarse-grained (CG) molecular dynamics (MD) simulations. The CG model is derived by adapting the Martini model for nonbonded interactions along with the Boltzmann inversion (BI) of bonded interactions from all-atom (AA) simulations. Our derived CG model successfully captures the experimentally observed micellar-, hexagonal-, lamellar-, and polymer-rich solution phase. The end-to-end distance reveals the conformational change from an open-chain structure in the micellar phase to a folded-chain structure in the lamellar phase, increasing the orientational order. An increase in temperature leads to expulsion of water molecules from the L64 moiety, suggesting an increase in L64 hydrophobicity. Thermodynamic analysis using the two-phase thermodynamics (2PT) method suggests the entropy of the system decreases with increasing L64 concentration and the decrease in free energy (F) with temperature is mainly driven by the entropic factor (-TS). Further, the increase in aggregation number at lower concentrations and self-assembly at very high concentrations is energetically driven, whereas the change from the micellar phase to the lamellar phase with increasing L64 concentration is entropically driven. Our model provides molecular insights into L64 phases which can be further explored to design functionality-based suprastructures for drug delivery and tissue engineering applications.
Collapse
Affiliation(s)
- Mangesh Bhendale
- Department of Chemical Engineering, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016, India
| | - Arpita Srivastava
- Department of Chemical Engineering, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016, India
| | - Jayant K Singh
- Department of Chemical Engineering, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.,Prescience Insilico Private Limited, Fifth Floor, Novel MSR Building, Marathahalli, Bengaluru, Karnataka 560037, India
| |
Collapse
|
|
18
|
Zhao Z, Li M, Zeng J, Huo L, Liu K, Wei R, Ni K, Gao J. Recent advances in engineering iron oxide nanoparticles for effective magnetic resonance imaging. Bioact Mater 2022; 12:214-245. [PMID: 35310380 PMCID: PMC8897217 DOI: 10.1016/j.bioactmat.2021.10.014] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 09/27/2021] [Accepted: 10/10/2021] [Indexed: 02/09/2023] Open
Abstract
Iron oxide nanoparticle (IONP) with unique magnetic property and high biocompatibility have been widely used as magnetic resonance imaging (MRI) contrast agent (CA) for long time. However, a review which comprehensively summarizes the recent development of IONP as traditional T2 CA and its new application for different modality of MRI, such as T1 imaging, simultaneous T2/T1 or MRI/other imaging modality, and as environment responsive CA is rare. This review starts with an investigation of direction on the development of high-performance MRI CA in both T2 and T1 modal based on quantum mechanical outer sphere and Solomon–Bloembergen–Morgan (SBM) theory. Recent rational attempts to increase the MRI contrast of IONP by adjusting the key parameters, including magnetization, size, effective radius, inhomogeneity of surrounding generated magnetic field, crystal phase, coordination number of water, electronic relaxation time, and surface modification are summarized. Besides the strategies to improve r2 or r1 values, strategies to increase the in vivo contrast efficiency of IONP have been reviewed from three different aspects, those are introducing second imaging modality to increase the imaging accuracy, endowing IONP with environment response capacity to elevate the signal difference between lesion and normal tissue, and optimizing the interface structure to improve the accumulation amount of IONP in lesion. This detailed review provides a deep understanding of recent researches on the development of high-performance IONP based MRI CAs. It is hoped to trigger deep thinking for design of next generation MRI CAs for early and accurate diagnosis.
T2 contrast capacity of iron oxide nanoparticles (IONPs) could be improved based on quantum mechanical outer sphere theory. IONPs could be expand to be used as effective T1 CAs by improving q value, extending τs, and optimizing interface structure. Environment responsive MRI CAs have been developed to improve the diagnosis accuracy. Introducing other imaging contrast moiety into IONPs could increase the contrast efficiency. Optimizing in vivo behavior of IONPs have been proved to enlarge the signal difference between normal tissue and lesion.
Collapse
|
|
19
|
Sarwar S, Abdul Qadir M, Alharthy RD, Ahmed M, Ahmad S, Vanmeert M, Mirza MU, Hameed A. Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-Fluorouracil. Molecules 2022; 27:1780. [PMID: 35335144 PMCID: PMC8954791 DOI: 10.3390/molecules27061780] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 02/25/2022] [Accepted: 03/04/2022] [Indexed: 01/01/2023] Open
Abstract
A targeted delivery system is primarily intended to carry a potent anticancer drug to specific tumor sites within the bodily tissues. In the present study, a carrier system has been designed using folic acid (FA), bis-amine polyethylene glycol (PEG), and an anticancer drug, 5-fluorouracil (5-FU). FA and PEG were joined via an amide bond, and the resulting FA-PEG-NH2 was coupled to 5-FU producing folate-polyethylene glycol conjugated 5-fluorouracil (FA-PEG-5-FU). Spectroscopic techniques (UV-Vis, 1HNMR, FTIR, and HPLC) were used for the characterization of products. Prodrug (FA-PEG-5-FU) was analyzed for drug release profile (in vitro) up to 10 days and compared to a standard anticancer drug (5-FU). Folate conjugate was also analyzed to study its folate receptors (FR) mediated transport and in vitro cytotoxicity assays using HeLa cancer cells/Vero cells, respectively, and antitumor activity in tumor-bearing mice models. Folate conjugate showed steady drug release patterns and improved uptake in the HeLa cancer cells than Vero cells. Folate conjugate treated mice group showed smaller tumor volumes; specifically after the 15th day post-treatment, tumor sizes were decreased significantly compared to the standard drug group (5-FU). Molecular docking findings demonstrated importance of Trp138, Trp140, and Lys136 in the stabilization of flexible loop flanking the active site. The folic acid conjugated probe has shown the potential of targeted drug delivery and sustained release of anticancer drug to tumor lesions with intact antitumor efficacy.
Collapse
Affiliation(s)
- Shabnam Sarwar
- School of Chemistry, University of the Punjab, Lahore 54590, Pakistan; (M.A.Q.); (S.A.)
| | - Muhammad Abdul Qadir
- School of Chemistry, University of the Punjab, Lahore 54590, Pakistan; (M.A.Q.); (S.A.)
| | - Rima D. Alharthy
- Chemistry Department, Faculty of Science and Arts, King Abdulaziz University, Rabigh 21911, Saudi Arabia
| | - Mahmood Ahmed
- Department of Chemistry, Division of Science and Technology, University of Education, College Road, Lahore 54770, Pakistan
| | - Saghir Ahmad
- School of Chemistry, University of the Punjab, Lahore 54590, Pakistan; (M.A.Q.); (S.A.)
| | - Michiel Vanmeert
- Medicinal Chemistry, Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium; (M.V.); (M.U.M.)
| | - Muhammad Usman Mirza
- Medicinal Chemistry, Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium; (M.V.); (M.U.M.)
- Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B 3P4, Canada
| | - Abdul Hameed
- Department of Chemistry, University of Sahiwal, Sahiwal 57000, Pakistan;
| |
Collapse
|
|
20
|
Wen D, Zhang X, Ding L, Wen H, Liu W, Zhang C, Wang B, Li L, Diao H. Folic acid functionalized aggregation-induced emission nanoparticles for tumor cell targeted imaging and photodynamic therapy. RSC Adv 2022; 12:4484-4489. [PMID: 35425471 PMCID: PMC8981163 DOI: 10.1039/d1ra09173e] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 01/29/2022] [Indexed: 12/21/2022] Open
Abstract
Recently, molecules with aggregation-induced luminescence (AIE) characteristics have received more and more attention due to the fluorescence of traditional dyes being easily quenched in the aggregated state. AIE molecules have significant advantages, such as excellent light stability, bright fluorescence, high contrast, and large Stokes shift. These characteristics have aroused wide interest of researchers and opened up new applications in many fields, especially in the field of biological applications. However, AIE molecules or their aggregates have certain limitations in multifunctional biological research due to their low specific targeting ability, poor biocompatibility, and poor stability in physiological body fluids. In order to overcome these problems, a novel nanoparticle, FFM1, was fabricated and characterized. FFM1 displayed good water solubility, biocompatibility, and AIE emission properties. It could target HeLa cells specifically by recognizing their folate receptor. Reactive oxygen triggered by light irradiation induced tumor cell apoptosis. Summarily, FFM1 displayed excellent capacity in target imaging and photodynamic killing of HeLa cells. It has shown potential application value in targeted diagnosis and photodynamic therapy of tumors, and has important guiding significance for the treatment of malignant tumors. It paves a way for the development of a novel strategy for tumor theranostics.
Collapse
Affiliation(s)
- Danning Wen
- Department of Biochemistry and Molecular Biology, Shanxi Medical University Taiyuan 030001 P. R. China
| | - Xueyun Zhang
- Department of Biochemistry and Molecular Biology, Shanxi Medical University Taiyuan 030001 P. R. China
| | - Lei Ding
- Department of Biochemistry and Molecular Biology, Shanxi Medical University Taiyuan 030001 P. R. China
| | - Huan Wen
- College of Basic Medical Sciences, Shanxi Medical University Taiyuan 030001 P. R. China
| | - Wen Liu
- Department of Biochemistry and Molecular Biology, Shanxi Medical University Taiyuan 030001 P. R. China
- College of Basic Medical Sciences, Shanxi Medical University Taiyuan 030001 P. R. China
| | - Chengwu Zhang
- College of Basic Medical Sciences, Shanxi Medical University Taiyuan 030001 P. R. China
| | - Bin Wang
- College of Basic Medical Sciences, Shanxi Medical University Taiyuan 030001 P. R. China
| | - Lihong Li
- Department of Biochemistry and Molecular Biology, Shanxi Medical University Taiyuan 030001 P. R. China
- College of Basic Medical Sciences, Shanxi Medical University Taiyuan 030001 P. R. China
| | - Haipeng Diao
- Department of Biochemistry and Molecular Biology, Shanxi Medical University Taiyuan 030001 P. R. China
- College of Basic Medical Sciences, Shanxi Medical University Taiyuan 030001 P. R. China
| |
Collapse
|
|
21
|
Puri V, Chaudhary KR, Singh A, Singh C. Inhalation potential of N-Acetylcysteine loaded PLGA nanoparticles for the management of tuberculosis: In vitro lung deposition and efficacy studies. CURRENT RESEARCH IN PHARMACOLOGY AND DRUG DISCOVERY 2022; 3:100084. [PMID: 35112077 PMCID: PMC8790477 DOI: 10.1016/j.crphar.2022.100084] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 01/06/2022] [Accepted: 01/12/2022] [Indexed: 12/28/2022] Open
Abstract
Several studies have stated that mucus is a critical hurdle for drug delivery to the mucosal tissues. As a result, Polymeric nanoparticles that can overcome mucus barriers are gaining popularity for controlled drug delivery into intra-macrophages to attain high intracellular drug concentration. The present study was aimed to fabricate inhalable N-acetylcysteine (NAC) modified PLGA mucus penetrating particles using the double emulsion method (w/o/w) for target delivery to alveolar macrophages and minimize the dose-related adverse effects, efficiently encapsulate hydrophilic drug, sustain the release profile and prolong the retention time for the management of tuberculosis. Among the numerous formulations, the drug/polymer ratio of 1:10 with 0.50% PVA concentration and sonication time for 2 min s was chosen for further research. The formulated nanoparticles had a mean particle size of 307.50 ± 9.54 nm, PDI was 0.136 ± 0.02, zeta potential about -11.3 ± 0.4 mV, decent entrapment efficiency (55.46 ± 2.40%), drug loading (9.05 ± 0.22%), and excellent flowability. FTIR confirmed that NAC and PLGA were compatible with each other. SEM graphs elucidated that the nanoparticles were spherically shaped with a slightly rough surface whereas TEM analysis ensured the nanometer size nanoparticles and coating of lipid over NPs surface. PXRD spectrum concluded the transformation of the drug from crystalline to amorphous state in the formulation. In vitro release pattern was biphasic started with burst release (64.67 ± 1.53% within 12hrs) followed by sustained release over 48hrs thus enabling the prolonged replenishing of NAC. In vitro lung deposition study pronounced that coated NAC-PLGA-MPPs showed favorable results in terms of emitted dose (86.67 ± 2.52%), MMAD value (2.57 ± 0.12 μm), GSD value (1.55 ± 0.11 μm), and FPF of 62.67 ± 2.08% for the deposition and targeting the lungs. Finally, in vitro efficacy studies demonstrated that NAC-PLGA-MPPs presented more prominent antibacterial activity against MTB H37Rv strain as compared to NAC. Hence, PLGA based particles could be a better strategy to deliver the NAC for lung targeting.
Collapse
Affiliation(s)
- Vishal Puri
- Department of Pharmaceutics, ISF College of Pharmacy, GT Road NH-95, Ghal Kalan, Moga, Punjab, 142001, India
| | - Kabi Raj Chaudhary
- Department of Pharmaceutics, ISF College of Pharmacy, GT Road NH-95, Ghal Kalan, Moga, Punjab, 142001, India
| | - Arti Singh
- Department of Pharmacology, ISF College of Pharmacy, GT Road NH-95, Ghal Kalan, Moga, Punjab, 142001, India
| | - Charan Singh
- Department of Pharmaceutics, ISF College of Pharmacy, GT Road NH-95, Ghal Kalan, Moga, Punjab, 142001, India
| |
Collapse
|
|
22
|
Singla P, Garg S, McClements J, Jamieson O, Peeters M, Mahajan RK. Advances in the therapeutic delivery and applications of functionalized Pluronics: A critical review. Adv Colloid Interface Sci 2022; 299:102563. [PMID: 34826745 DOI: 10.1016/j.cis.2021.102563] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 10/15/2021] [Accepted: 11/13/2021] [Indexed: 12/22/2022]
Abstract
Pluronic (PEO-PPO-PEO) block copolymers can form nano-sized micelles with a structure composed of a hydrophobic PPO core and hydrophilic PEO shell layer. Pluronics are U.S. Food and Drug Administration approved polymers, which are widely used for solubilization of drugs and their delivery, gene/therapeutic delivery, diagnostics, and tissue engineering applications due to their non-ionic properties, non-toxicity, micelle forming ability, excellent biocompatibility and biodegradability. Although Pluronics have been employed as drug carrier systems for several decades, numerous issues such as rapid dissolution, shorter residence time in biological media, fast clearance and weak mechanical strength have hindered their efficacy. Pluronics have been functionalized with pH-sensitive, biological-responsive moieties, antibodies, aptamers, folic acid, drugs, different nanoparticles, and photo/thermo-responsive hydrogels. These functionalization strategies enable Pluronics to act as stimuli responsive and targeted drug delivery vehicles. Moreover, Pluronics have emerged in nano-emulsion formulations and have been utilized to improve the properties of cubosomes, dendrimers and nano-sheets, including their biocompatibility and aqueous solubility. Functionalization of Pluronics results in the significant improvement of target specificity, loading capacity, biocompatibility of nanoparticles and stimuli responsive hydrogels for the promising delivery of a range of drugs. Therefore, this review presents an overview of all advancements (from the last 15 years) in functionalized Pluronics, providing a valuable tool for industry and academia in order to optimize their use in drug or therapeutic delivery, in addition to several other biomedical applications.
Collapse
Affiliation(s)
- Pankaj Singla
- School of Engineering, Merz Court, Claremont Road, Newcastle University, Newcastle Upon Tyne NE1 7RU, United Kingdom
| | - Saweta Garg
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, India
| | - Jake McClements
- School of Engineering, Merz Court, Claremont Road, Newcastle University, Newcastle Upon Tyne NE1 7RU, United Kingdom
| | - Oliver Jamieson
- School of Engineering, Merz Court, Claremont Road, Newcastle University, Newcastle Upon Tyne NE1 7RU, United Kingdom
| | - Marloes Peeters
- School of Engineering, Merz Court, Claremont Road, Newcastle University, Newcastle Upon Tyne NE1 7RU, United Kingdom.
| | - Rakesh Kumar Mahajan
- Department of Chemistry, UGC-Centre for Advanced Studies-I, Guru Nanak Dev University, Amritsar 143005, India.
| |
Collapse
|
|
23
|
Zivarpour P, Hallajzadeh J, Asemi Z, Sadoughi F, Sharifi M. Chitosan as possible inhibitory agents and delivery systems in leukemia. Cancer Cell Int 2021; 21:544. [PMID: 34663339 PMCID: PMC8524827 DOI: 10.1186/s12935-021-02243-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 10/03/2021] [Indexed: 12/29/2022] Open
Abstract
Leukemia is a lethal cancer in which white blood cells undergo proliferation and immature white blood cells are seen in the bloodstream. Without diagnosis and management in early stages, this type of cancer can be fatal. Changes in protooncogenic genes and microRNA genes are the most important factors involved in development of leukemia. At present, leukemia risk factors are not accurately identified, but some studies have pointed out factors that predispose to leukemia. Studies show that in the absence of genetic risk factors, leukemia can be prevented by reducing the exposure to risk factors of leukemia, including smoking, exposure to benzene compounds and high-dose radioactive or ionizing radiation. One of the most important treatments for leukemia is chemotherapy which has devastating side effects. Chemotherapy and medications used during treatment do not have a specific effect and destroy healthy cells besides leukemia cells. Despite the suppressing effect of chemotherapy against leukemia, patients undergoing chemotherapy have poor quality of life. So today, researchers are focusing on finding more safe and effective natural compounds and treatments for cancer, especially leukemia. Chitosan is a valuable natural compound that is biocompatible and non-toxic to healthy cells. Anticancer, antibacterial, antifungal and antioxidant effects are examples of chitosan biopolymer properties. The US Food and Drug Administration has approved the use of this compound in medical treatments and the pharmaceutical industry. In this article, we take a look at the latest advances in the use of chitosan in the treatment and improvement of leukemia.
Collapse
Affiliation(s)
- Parinaz Zivarpour
- Department of Biological Sciences, Faculty of Basic Sciences, Higher Education Institute of Rab-Rashid, Tabriz, Iran
| | - Jamal Hallajzadeh
- Department of Biochemistry and Nutrition, Research Center for Evidence-Based Health Management, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Fatemeh Sadoughi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Mehran Sharifi
- Department of Internal Medicine, School of Medicine, Cancer Prevention Research Center, Seyyed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| |
Collapse
|
|
24
|
Recent trends in design and evaluation of chitosan-based colon targeted drug delivery systems: Update 2020. J Drug Deliv Sci Technol 2021. [DOI: 10.1016/j.jddst.2021.102579] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
|
|
25
|
Advances in Functionalized Photosensitive Polymeric Nanocarriers. Polymers (Basel) 2021; 13:polym13152464. [PMID: 34372067 PMCID: PMC8348146 DOI: 10.3390/polym13152464] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 06/30/2021] [Accepted: 07/01/2021] [Indexed: 02/06/2023] Open
Abstract
The synthesis of light-responsive nanocarriers (LRNs) with a variety of surface functional groups and/or ligands has been intensively explored for space-temporal controlled cargo release. LRNs have been designed on demand for photodynamic-, photothermal-, chemo-, and radiotherapy, protected delivery of bioactive molecules, such as smart drug delivery systems and for theranostic duties. LRNs trigger the release of cargo by a light stimulus. The idea of modifying LRNs with different moieties and ligands search for site-specific cargo delivery imparting stealth effects and/or eliciting specific cellular interactions to improve the nanosystems’ safety and efficacy. This work reviews photoresponsive polymeric nanocarriers and photo-stimulation mechanisms, surface chemistry to link ligands and characterization of the resultant nanosystems. It summarizes the interesting biomedical applications of functionalized photo-controlled nanocarriers, highlighting the current challenges and opportunities of such high-performance photo-triggered delivery systems.
Collapse
|
|
26
|
Sánchez J, Rodríguez-Reyes M, Cortés-Hernández DA, Ávila-Orta CA, Reyes-Rodríguez PY. Heating capacity and biocompatibility of Pluronic-coated manganese gallium ferrites for magnetic hyperthermia treatment. Colloids Surf A Physicochem Eng Asp 2021. [DOI: 10.1016/j.colsurfa.2020.125986] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
|
|
27
|
Liu F, Chen B, Chen W, Chen S, Ma D, Xie M. Preparation of FA-targeted magnetic nanocomposites co-loading TFPI-2 plasmid and cis-platinum and its targeted therapy effects on nasopharyngeal carcinoma. Int J Med Sci 2021; 18:2355-2365. [PMID: 33967612 PMCID: PMC8100641 DOI: 10.7150/ijms.52643] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 03/16/2021] [Indexed: 11/05/2022] Open
Abstract
The majority of patients diagnosed with nasopharyngeal carcinoma (NPC) present with advanced-stage disease. The main treatment for these patients is concurrent chemoradiotherapy, which has various side effects. To improve the therapeutic effects and reduce the side effects of NPC chemoradiotherapy, we constructed a multifunctional folic acid (FA)-targeted magnetic nanocomposite codelivering tissue factor pathway inhibitor-2 (TFPI-2) and cisplatin (CDDP). This novel nanocomposite (FA-MNP/CDDP/TFPI-2) was obtained by amidation and electrostatic adsorption between FA-methoxypolyethylene glycol-polyethyleneimine (FA-MPEG-PEI) containing the TFPI-2 plasmid and magnetic nanoparticles modified by aldehyde sodium alginate loaded with CDDP. Transmission electron microscopy (TEM) images showed that the size of the individual magnetite particle core was approximately 11.5 nm. The structure and composition of the nanocomposites were identified and examined by 1H nuclear magnetic resonance (NMR) spectroscopy and ultraviolet (UV) spectrophotometry. The fluorescence analysis, Prussian blue iron staining, magnetic resonance (MR) imaging and whole-body fluorescence imaging results demonstrated that FA-MNP/CDDP/TFPI-2 showed high gene transfection efficiency and could target tumor cells via folate receptor (FR)-mediated delivery. The codelivery analysis showed that the obtained FA-MNP/CDDP/TFPI-2 composite could cause significantly more apoptosis than treatment with CDDP or TFPI-2 alone. The results showed that the FA-MNP/CDDP/TFPI-2 composites were successfully synthesized and indicated to be a specific molecular target for the FR with significant inhibitory effects on the growth of HNE-1 cells.
Collapse
Affiliation(s)
- Fang Liu
- Department of Otorhinolaryngology Head and Neck Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China
| | - Bojie Chen
- Department of Joint Surgery, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, 341000, China
| | - Weifeng Chen
- Department of Otorhinolaryngology Head and Neck Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China
| | - Shuaijun Chen
- Department of Otolaryngology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
| | - Dong Ma
- Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering,Jinan University, Guangzhou, 510632, China
| | - Minqiang Xie
- Department of Otolaryngology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
| |
Collapse
|
|
28
|
Zhou Y, Yu Y, Ma D, Foucher AC, Xiong L, Zhang J, Stach EA, Yue Q, Kang Y. Atomic Fe Dispersed Hierarchical Mesoporous Fe–N–C Nanostructures for an Efficient Oxygen Reduction Reaction. ACS Catal 2020. [DOI: 10.1021/acscatal.0c03496] [Citation(s) in RCA: 72] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- Yu Zhou
- Institute of Fundamental and Frontier Science, University of Electronic Science and Technology of China, Chengdu 610054, China
| | - Yanan Yu
- Institute of Fundamental and Frontier Science, University of Electronic Science and Technology of China, Chengdu 610054, China
| | - Dongsheng Ma
- Institute of Fundamental and Frontier Science, University of Electronic Science and Technology of China, Chengdu 610054, China
| | - Alexandre C. Foucher
- Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
| | - Lei Xiong
- Institute of Fundamental and Frontier Science, University of Electronic Science and Technology of China, Chengdu 610054, China
| | - Jiahao Zhang
- Institute of Fundamental and Frontier Science, University of Electronic Science and Technology of China, Chengdu 610054, China
| | - Eric A. Stach
- Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
| | - Qin Yue
- Institute of Fundamental and Frontier Science, University of Electronic Science and Technology of China, Chengdu 610054, China
| | - Yijin Kang
- Institute of Fundamental and Frontier Science, University of Electronic Science and Technology of China, Chengdu 610054, China
| |
Collapse
|
|
29
|
Li D, Hu C, Yang J, Liao Y, Chen Y, Fu SZ, Wu JB. Enhanced Anti-Cancer Effect of Folate-Conjugated Olaparib Nanoparticles Combined with Radiotherapy in Cervical Carcinoma. Int J Nanomedicine 2020; 15:10045-10058. [PMID: 33328733 PMCID: PMC7735794 DOI: 10.2147/ijn.s272730] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 11/17/2020] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Radiotherapy (RT), one of the main treatments for cervical cancer, has tremendous potential for improvement in the efficacy. Poly (ADP-ribose) polymerase (PARP) is a key enzyme in the repair of DNA strand breaks (DSB). Olaparib (Ola) is a PARP inhibitor that is involved in preventing the release of PARP from RT-induced damaged DNA to potentiate the effect of RT. Although the basic mechanism of Ola's radiosensitization is well known, the radiosensitization mechanism of its nanomedicine is still unclear. In addition, the lack of tumor tissue targeting is a major obstacle for the clinical success of Ola. MATERIALS AND METHODS In this study, we developed folate-conjugated active targeting olaparib nanoparticles (ATO) and investigated the anti-tumor effect of ATO combined with radiotherapy (RT) in nude mice using cervical cancer xenograft models. We used folate (FA)-conjugated poly (ε-caprolactone)-poly (ethyleneglycol)-poly (e-caprolactone) (PCEC) copolymer to prepare ATO via emulsification/solvent diffusion. Further, we evaluated ATO particle size, potential, encapsulation efficiency, and in vitro release characteristics, and evaluated the shape of ATO via transmission electron microscopy (TEM). We then performed MTT and cell uptake assays to detect cytotoxicity and targeting uptake in vitro. We investigated the anti-tumor properties of ATO in vivo by apoptosis test, 18 F-FDG PET/CT, and immunohistochemical analysis. Finally, the xenografted tumor in nude mice was subjected to RT and/or ATO treatment. RESULTS The results confirmed that ATO in combination with RT significantly inhibited tumor growth and prolonged survival time of tumor-bearing mice. This may be related to the inhibition of tumor proliferation and DNA damage repair and induction of cell apoptosis in vivo. CONCLUSION The ATO developed in this study may represent a novel formulation for olaparib delivery and have promising potential for treating tumors with an over-expression of folate receptors.
Collapse
Affiliation(s)
- Dong Li
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
| | - Chuanfei Hu
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
| | - Juan Yang
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
| | - Yin Liao
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
| | - Yue Chen
- Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
| | - Shao Zhi Fu
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
| | - Jing Bo Wu
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou646000, People’s Republic of China
| |
Collapse
|
|
30
|
Li X, Ma Y, Zhong XL, Wang LS. Silver sulfide nanoparticles on MWCNTs stabilized by poloxamer: An enhanced electrochemical sensor for high sensitivity detection of 2,4,6-trinitrotoluene. Microchem J 2020. [DOI: 10.1016/j.microc.2020.105488] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
|
|
31
|
Physicochemical Characterization of PHBV Nanoparticles Functionalized with Multiple Bioactives Designed to be Theranostics for Lung Cancer. J CLUST SCI 2020. [DOI: 10.1007/s10876-020-01912-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
|
|
32
|
Kumar R, Mondal K, Panda PK, Kaushik A, Abolhassani R, Ahuja R, Rubahn HG, Mishra YK. Core-shell nanostructures: perspectives towards drug delivery applications. J Mater Chem B 2020; 8:8992-9027. [PMID: 32902559 DOI: 10.1039/d0tb01559h] [Citation(s) in RCA: 94] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Nanosystems have shown encouraging outcomes and substantial progress in the areas of drug delivery and biomedical applications. However, the controlled and targeted delivery of drugs or genes can be limited due to their physicochemical and functional properties. In this regard, core-shell type nanoparticles are promising nanocarrier systems for controlled and targeted drug delivery applications. These functional nanoparticles are emerging as a particular class of nanosystems because of their unique advantages, including high surface area, and easy surface modification and functionalization. Such unique advantages can facilitate the use of core-shell nanoparticles for the selective mingling of two or more different functional properties in a single nanosystem to achieve the desired physicochemical properties that are essential for effective targeted drug delivery. Several types of core-shell nanoparticles, such as metallic, magnetic, silica-based, upconversion, and carbon-based core-shell nanoparticles, have been designed and developed for drug delivery applications. Keeping the scope, demand, and challenges in view, the present review explores state-of-the-art developments and advances in core-shell nanoparticle systems, the desired structure-property relationships, newly generated properties, the effects of parameter control, surface modification, and functionalization, and, last but not least, their promising applications in the fields of drug delivery, biomedical applications, and tissue engineering. This review also supports significant future research for developing multi-core and shell-based functional nanosystems to investigate nano-therapies that are needed for advanced, precise, and personalized healthcare systems.
Collapse
Affiliation(s)
- Raj Kumar
- Faculty of Engineering and Institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan-52900, Israel.
| | - Kunal Mondal
- Materials Science and Engineering Department, Idaho National Laboratory, Idaho Falls, ID 83415, USA.
| | - Pritam Kumar Panda
- Condensed Matter Theory Group, Materials Theory Division, Department of Physics and Astronomy, Uppsala University, Box 516, SE-75120, Uppsala, Sweden
| | - Ajeet Kaushik
- NanoBioTech Laboratory, Department of Natural Sciences, Division of Sciences, Art, & Mathematics, Florida Polytechnic University, Lakeland, FL-33805, USA
| | - Reza Abolhassani
- Mads Clausen Institute, NanoSYD, University of Southern Denmark, Alsion 2, DK-6400, Sønderborg, Denmark.
| | - Rajeev Ahuja
- Condensed Matter Theory Group, Materials Theory Division, Department of Physics and Astronomy, Uppsala University, Box 516, SE-75120, Uppsala, Sweden and Applied Materials Physics, Department of Materials Science and Engineering, Royal Institute of Technology (KTH), SE-10044 Stockholm, Sweden
| | - Horst-Günter Rubahn
- Mads Clausen Institute, NanoSYD, University of Southern Denmark, Alsion 2, DK-6400, Sønderborg, Denmark.
| | - Yogendra Kumar Mishra
- Mads Clausen Institute, NanoSYD, University of Southern Denmark, Alsion 2, DK-6400, Sønderborg, Denmark.
| |
Collapse
|
|
33
|
Linley S, Thomson NR, McVey K, Sra K, Gu FX. Factors affecting pluronic-coated iron oxide nanoparticle binding to petroleum hydrocarbon-impacted sediments. CHEMOSPHERE 2020; 254:126732. [PMID: 32320831 DOI: 10.1016/j.chemosphere.2020.126732] [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: 11/01/2019] [Revised: 04/02/2020] [Accepted: 04/05/2020] [Indexed: 06/11/2023]
Abstract
Effective targeted delivery of nanoparticle agents may enhance the remediation of soils and site characterization efforts. Nanoparticles coated with Pluronic, an amphiphilic block co-polymer, demonstrated targeted binding behaviour toward light non-aqueous phase liquids such as heavy crude oil. Various factors including coating concentration, oil concentration, oil type, temperature, and pH were assessed to determine their effect on nanoparticle binding to heavy crude oil-impacted sandy aquifer material. Nanoparticle binding was increased by decreasing the coating concentration, increasing oil concentration, using heavier oil types, and increasing temperature, while pH over the range of 5-9 was found to have no effect. Nanoparticle transport and binding in columns packed with clean and oily porous media demonstrated the ability for efficient nanoparticle targeted binding. For the conditions explored, the attachment rate coefficient in columns packed with clean sand was 2.10 ± 0.66 × 10-4 s-1; however, for columns packed with oil-impacted sand a minimum attachment rate coefficient of 8.86 ± 0.43 × 10-4 s-1 was estimated. The higher attachment rate for the oil-impacted sand system indicates that nanoparticles may preferentially accumulate to oil-impacted zones present at heterogeneous impacted sites. Simulations were used to demonstrate this hypothesis using the set of parameters generated in this effort. This work contributes to our understanding of the application conditions that are required for efficient targeted binding of nanoparticles to crude-oil impacted porous media.
Collapse
Affiliation(s)
- Stuart Linley
- Department of Civil & Environmental Engineering, University of Waterloo, Waterloo, Ontario, Canada; Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Ontario, Canada.
| | - Neil R Thomson
- Department of Civil & Environmental Engineering, University of Waterloo, Waterloo, Ontario, Canada
| | - Kevin McVey
- Chevron Energy Technology Company, Houston, TX, USA
| | | | - Frank X Gu
- Department of Chemical Engineering & Applied Chemistry, University of Toronto, Toronto, Ontario, Canada
| |
Collapse
|
|
34
|
Suciu M, Ionescu CM, Ciorita A, Tripon SC, Nica D, Al-Salami H, Barbu-Tudoran L. Applications of superparamagnetic iron oxide nanoparticles in drug and therapeutic delivery, and biotechnological advancements. BEILSTEIN JOURNAL OF NANOTECHNOLOGY 2020; 11:1092-1109. [PMID: 32802712 PMCID: PMC7404288 DOI: 10.3762/bjnano.11.94] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Accepted: 07/07/2020] [Indexed: 05/13/2023]
Abstract
Superparamagnetic iron oxide nanoparticles (SPIONs) have unique properties with regard to biological and medical applications. SPIONs have been used in clinical settings although their safety of use remains unclear due to the great differences in their structure and in intra- and inter-patient absorption and response. This review addresses potential applications of SPIONs in vitro (formulations), ex vivo (in biological cells and tissues) and in vivo (preclinical animal models), as well as potential biomedical applications in the context of drug targeting, disease treatment and therapeutic efficacy, and safety studies.
Collapse
Affiliation(s)
- Maria Suciu
- Department of Molecular Biology and Biotechnology, Electron Microscopy Laboratory, Biology and Geology Faculty, Babes-Bolyai University, 5–7 Clinicilor Str., Cluj-Napoca, Cluj County, 400006, Romania
- Electron Microscopy Integrated Laboratory, National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donath Str., Cluj-Napoca, Cluj County, 400293, Romania
| | - Corina M Ionescu
- Department of Molecular Biology and Biotechnology, Electron Microscopy Laboratory, Biology and Geology Faculty, Babes-Bolyai University, 5–7 Clinicilor Str., Cluj-Napoca, Cluj County, 400006, Romania
| | - Alexandra Ciorita
- Department of Molecular Biology and Biotechnology, Electron Microscopy Laboratory, Biology and Geology Faculty, Babes-Bolyai University, 5–7 Clinicilor Str., Cluj-Napoca, Cluj County, 400006, Romania
- Electron Microscopy Integrated Laboratory, National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donath Str., Cluj-Napoca, Cluj County, 400293, Romania
| | - Septimiu C Tripon
- Department of Molecular Biology and Biotechnology, Electron Microscopy Laboratory, Biology and Geology Faculty, Babes-Bolyai University, 5–7 Clinicilor Str., Cluj-Napoca, Cluj County, 400006, Romania
- Electron Microscopy Integrated Laboratory, National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donath Str., Cluj-Napoca, Cluj County, 400293, Romania
| | - Dragos Nica
- Functional Sciences Department, Medical Faculty, University of Medicine and Pharmacy “Victor Babes”, 2 Eftimie Murgu, Timisoara, Timis County, 300041, Romania
| | - Hani Al-Salami
- Biotechnology and Drug Development Research Laboratory, the School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, GPO Box U1987, Perth Western Australia 6845, Australia
| | - Lucian Barbu-Tudoran
- Department of Molecular Biology and Biotechnology, Electron Microscopy Laboratory, Biology and Geology Faculty, Babes-Bolyai University, 5–7 Clinicilor Str., Cluj-Napoca, Cluj County, 400006, Romania
- Electron Microscopy Integrated Laboratory, National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donath Str., Cluj-Napoca, Cluj County, 400293, Romania
| |
Collapse
|
|
35
|
Jiang Y, Wang C, Zhang M, Fei X, Gu Y. Type and size effect of functional groups on the novel antifolate target recognition folate receptors α and β: Docking, molecular dynamics and MM/PBSA study. J Mol Graph Model 2020; 100:107663. [PMID: 32659629 DOI: 10.1016/j.jmgm.2020.107663] [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: 03/01/2020] [Revised: 05/23/2020] [Accepted: 05/26/2020] [Indexed: 11/19/2022]
Abstract
A series of novel antifolates (32 compounds) were used to study the interactions with folate receptors α and β. The compounds had different sizes of methyl (-CH3), carboxyl (-COOH), hydroxyl (-OH), and amino groups (-NH2). The binding properties of the complexes were studied by molecular docking, molecular dynamic (MD) simulations, and MM/PBSA free energy calculations. The docked binding energies and modes were analyzed to identify compounds with good recognition of FRα from FRβ. The stable conformers, root mean square displacement, root mean square fluctuation free binding energy, and contribution of residues to the binding energy of the complexes were further analyzed to illustrate the interactions between the novel compounds and folate receptors. The data show that introducing long functional groups in folate will increase the binding affinity with FRα but will decrease the binding affinity with FRβ. The results provide a strategy for the design of novel antifolates targeted to FRα.
Collapse
Affiliation(s)
- Yue Jiang
- School of Science, TianJin ChengJian University, Tianjin, China
| | - Cuihong Wang
- School of Science, TianJin ChengJian University, Tianjin, China.
| | - Meiling Zhang
- School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, China
| | - Xuening Fei
- School of Science, TianJin ChengJian University, Tianjin, China.
| | - Yingchun Gu
- School of Science, TianJin ChengJian University, Tianjin, China
| |
Collapse
|
|
36
|
Miranda MA, Silva LB, Carvalho IPS, Amaral R, de Paula MH, Swiech K, Bastos JK, Paschoal JAR, Emery FS, Dos Reis RB, Bentley MVLB, Marcato PD. Targeted uptake of folic acid-functionalized polymeric nanoparticles loading glycoalkaloidic extract in vitro and in vivo assays. Colloids Surf B Biointerfaces 2020; 192:111106. [PMID: 32474325 DOI: 10.1016/j.colsurfb.2020.111106] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Revised: 04/23/2020] [Accepted: 04/30/2020] [Indexed: 12/19/2022]
Abstract
Solanum lycocarpum fruits contain two major glycoalkaloids (GAs), solamargine (SM) and solasonine (SS). These compounds are reported as cytotoxic. However, they have poor water solubility and low bioavailability. To overcome these disadvantages and getting an efficient formulation the current study aimed to develop, characterize, and test the effectiveness of a nanotechnology-based strategy using poly(D,L-lactide) (PLA) nanoparticles functionalized with folate as delivery system of glycoalkaloidic extract (AE) for bladder cancer therapy. The strategic of adding folic acid into nanoformulations can increase the selectivity of the compounds to the cancer cells reducing the side effects. Our results revealed the successful preparation of AE-loaded folate-targeted nanoparticles (NP-F-AE) with particle size around 177 nm, negative zeta potential, polydispersity index <0.20, and higher efficiency of encapsulation for both GAs present in the extract (>85 %). To investigate the cellular uptake, the fluorescent dye coumarin-6 was encapsulated into the nanoparticle (NP-F-C6). The cell studies showed high uptake of nanoparticles by breast (MDA-MB-231) and bladder (RT4) cancer cells, but not for normal keratinocytes cells (HaCaT) indicating the target uptake to cancer cells. The cytotoxicity of nanoparticles was evaluated on RT4 2D culture model showing 2.16-fold lower IC50 than the free AE. Furthermore, the IC50 increased on the RT4 spheroids compared to 2D model. The nanoparticles penetrated homogeneously into the urotheliumof porcine bladder. These results showed that folate-conjugated polymeric nanoparticles are potential carriers for targeted glycoalkaloidic extract delivery to bladder cancer cells.
Collapse
Affiliation(s)
- M A Miranda
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - L B Silva
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - I P S Carvalho
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - R Amaral
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - M H de Paula
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - K Swiech
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - J K Bastos
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - J A R Paschoal
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - F S Emery
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - R B Dos Reis
- Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - M V L B Bentley
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - P D Marcato
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
| |
Collapse
|
|
37
|
Ghasemi Goorbandi R, Mohammadi MR, Malekzadeh K. Synthesizing efficacious genistein in conjugation with superparamagnetic Fe 3O 4 decorated with bio-compatible carboxymethylated chitosan against acute leukemia lymphoma. Biomater Res 2020; 24:9. [PMID: 32206338 PMCID: PMC7082912 DOI: 10.1186/s40824-020-00187-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Accepted: 02/28/2020] [Indexed: 01/11/2023] Open
Abstract
Background Genistein (C15H10O5) is a soy isoflavone with anti-cancer properties such as inhibition of cell growth, proliferation and tumor invasion, but effective dosage against hematopoietic malignant cells was not in non-toxic range. This property cause to impede its usage as chemotherapeutic agent. Therefore, this hypothesis raised that synthesizing biocompatible nanoparticle could assist to prevail this struggle. Methods Genistein covalently attached on Fe3O4 nanoparticles decorated with carboxymethylated chitosan to fabricate Fe3O4-CMC-genistein in alkaline circumstance. This obtained nanoparticles were evaluated by TEM, DLS, FTIR, XRD and VSM and its anti-cancer effect by growth rate and MTT assays as well as flow cytometer on ALL cancer cell lines. Results Different evaluations indicated that the drug delivery vehicle had a mean diameter size around 12ƞm with well bounded components. This system presented high degree of magnetization and superparamagnetic properties as well as good water solubility. In comparison with pure genistein, significant growth inhibition on hematopoietic cancer cells in lower dose of genistein nano-conjugated onto Fe3O4-CMC. It increased long lasting effect of genistein in cancer cells also. Conclusion This delivery system for genistein could be remarkably promised and futuristic as biocompatible chemotherapeutic agent against hematopoietic malignant cells.
Collapse
Affiliation(s)
- Rachel Ghasemi Goorbandi
- 1Sharif University of Technology, Kish International Campus, Kish Island, Iran.,2Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Mohammad Reza Mohammadi
- 4Department of Medical Genetics; Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Kianoosh Malekzadeh
- 2Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.,3Department of Materials Science and Engineering, Sharif University of Technology, Tehran, Iran
| |
Collapse
|
|
38
|
Ding L, Wang R, Hu Y, Xu F, Zhang N, Cao X, Wang X, Shi X, Guo R. Folic acid-modified Laponite®-stabilized Fe3O4 nanoparticles for targeted T-weighted MR imaging of tumor. APPLIED CLAY SCIENCE 2020; 186:105447. [DOI: 10.1016/j.clay.2020.105447] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
39
|
Li Z, Xiong X, Peng S, Chen X, Liu W, Liu C. Novel folated pluronic F127 modified liposomes for delivery of curcumin: preparation, release, and cytotoxicity. J Microencapsul 2020; 37:220-229. [PMID: 32039640 DOI: 10.1080/02652048.2020.1720030] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Aim: A novel folated pluronic F127 (FA-F127) was synthesised, so as to modify liposomes with FA group on the surface, and evaluate the effects of FA-F127 modification on the properties of the modified liposomes.Methods: FA was linked to one end of pluronic F127, via the terminal OH group, to obtain FA-F127 and the structure was characterised. FA-F127 modified curcumin liposomes (cur-FA-F127-Lps) were prepared. The physicochemical characteristics of cur-FA-F127-Lps, including morphology and particle size, were studied. The in vitro cytotoxicity of cur-FA-F127-Lps against KB cancer cells was determined by MTT tests.Results: The effects of FA-F127 modification on the average particle size, PDI, curcumin encapsulation efficiency and microstructure were not significant. Compared with nonfolated F127 liposomes (cur-F127-Lps), cur-FA-F127-Lps exhibited significantly higher cytotoxicity towards KB cells.Conclusions: Folic acid modified liposomes provide a novel strategy to improve the chemotherapeutic efficacy of hydrophobic bioactive compounds.
Collapse
Affiliation(s)
- Ziling Li
- School of Life Science, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi, PR China.,State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, PR China
| | - Xiangyuan Xiong
- School of Life Science, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi, PR China
| | - Shengfeng Peng
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, PR China
| | - Xing Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, PR China
| | - Wei Liu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, PR China.,National R&D Center for Freshwater Fish Processing, Jiangxi Normal University, Nanchang, Jiangxi, PR China
| | - Chengmei Liu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, PR China
| |
Collapse
|
|
40
|
Iron oxide nanoparticle core-shell magnetic microspheres: Applications toward targeted drug delivery. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2020; 24:102134. [DOI: 10.1016/j.nano.2019.102134] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Revised: 11/19/2019] [Accepted: 11/19/2019] [Indexed: 12/27/2022]
|
|
41
|
Fei MY, Song MM, Wang P, Pang GZ, Chen J, Lu DP, Liu R, Zhang GY, Zhao TT, Shen YX, Yu YQ. Folic acid modified Fe 3O 4 nanoclusters by a one-step ultrasonic technique for drug delivery and MR imaging. RSC Adv 2020; 10:5294-5303. [PMID: 35498332 PMCID: PMC9049288 DOI: 10.1039/c9ra09670a] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 01/17/2020] [Indexed: 11/24/2022] Open
Abstract
Multifunctional nanoclusters based on Fe3O4 nanoparticles for magnetic resonance imaging (MRI) and drug delivery are reported here. At first, oleic acid (OA)-coated Fe3O4 nanoparticles were prepared. Then block copolymer Pluronic F127 or folic acid (FA) conjugated-Pluronic F127 was used to modify the hydrophobic nanoparticles to become hydrophilic Fe3O4@F127 nanoclusters via facile ultrasonic treatment. During this process, drug molecules can also be introduced into the nanoclusters and therefore the targeted drug delivery system was formed. Next, we verified the feasibility of the nanoclusters as drug delivery vehicles and magnetic contrast agents. The nanoclusters have an average size of 200 nm and remained stable in water for long periods. Folic acid-modified nanoclusters showed an enhanced intracellular uptake into HepG2 cells by using both cellular iron amount analysis and flow cytometry analysis. Besides, Fe3O4@F127@FA nanoclusters showed good compatibility in the tested concentration range and good sensitivity in T2-weighted MRI. The magnetic nanoclusters combined with drug delivery properties have greatly increased the significance in the diagnosis and therapy of diseases, which are suitable for systematical administration of hydrophobic drugs and simultaneously MRI diagnosis. Water-soluble Fe3O4@F127@FA nanoclusters were prepared by a facile ultrasonic-treated method for MR imaging and targeted drug delivery.![]()
Collapse
Affiliation(s)
- Meng-Yu Fei
- The First Affiliated Hospital, Anhui Medical University 218 Jixi Road Hefei Anhui PR China +86-551-62922381
| | - Meng-Meng Song
- School of Basic Medical Sciences, Anhui Medical University 81 Meishan Road Hefei Anhui PR China +86-551-65113776.,Biopharmaceutical Institute, Anhui Medical University 81 Meishan Road 230032 Hefei China
| | - Pei Wang
- School of Basic Medical Sciences, Anhui Medical University 81 Meishan Road Hefei Anhui PR China +86-551-65113776.,Biopharmaceutical Institute, Anhui Medical University 81 Meishan Road 230032 Hefei China
| | - Gao-Zong Pang
- School of Basic Medical Sciences, Anhui Medical University 81 Meishan Road Hefei Anhui PR China +86-551-65113776.,Biopharmaceutical Institute, Anhui Medical University 81 Meishan Road 230032 Hefei China
| | - Jing Chen
- School of Basic Medical Sciences, Anhui Medical University 81 Meishan Road Hefei Anhui PR China +86-551-65113776
| | - Da-Peng Lu
- School of Pharmacy, Anhui Medical University 81 Meishan Road Hefei Anhui PR China
| | - Rui Liu
- School of Basic Medical Sciences, Anhui Medical University 81 Meishan Road Hefei Anhui PR China +86-551-65113776
| | - Gui-Yang Zhang
- School of Basic Medical Sciences, Anhui Medical University 81 Meishan Road Hefei Anhui PR China +86-551-65113776
| | - Ting-Ting Zhao
- School of Basic Medical Sciences, Anhui Medical University 81 Meishan Road Hefei Anhui PR China +86-551-65113776
| | - Yu-Xian Shen
- School of Basic Medical Sciences, Anhui Medical University 81 Meishan Road Hefei Anhui PR China +86-551-65113776.,Biopharmaceutical Institute, Anhui Medical University 81 Meishan Road 230032 Hefei China
| | - Yong-Qiang Yu
- The First Affiliated Hospital, Anhui Medical University 218 Jixi Road Hefei Anhui PR China +86-551-62922381
| |
Collapse
|
|
42
|
Peerzade SAMA, Qin X, Laroche FJ, Palantavida S, Dokukin M, Feng H, Sokolov I. Ultrabright fluorescent silica nanoparticles for in vivo targeting of xenografted human tumors and cancer cells in zebrafish. NANOSCALE 2019; 11:22316-22327. [PMID: 31724677 PMCID: PMC7384872 DOI: 10.1039/c9nr06371d] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
New ultrabright fluorescent silica nanoparticles capable of the fast targeting of epithelial tumors in vivo are presented. The as-synthesized folate-functionalized ultrabright particles of 30-40 nm are 230 times brighter than quantum dots (QD450) and 50% brighter than the polymer dots with similar spectra (excitation 365 nm and emission 486 nm). To decrease non-specific targeting, particles are coated with polyethylene glycol (PEG). We demonstrate the in vivo targeting of xenographic human cervical epithelial tumors (HeLa cells) using zebrafish as a model system. The particles target tumors (and probably even individual HeLa cells) as small as 10-20 microns within 20-30 minutes after blood injection. To demonstrate the advantages of ultrabrightness, we repeated the experiments with similar but 200× less bright particles. Compared to those, ultrabright particles showed ∼3× faster tumor detection and ∼2× higher relative fluorescent contrast of tumors/cancer cells.
Collapse
Affiliation(s)
| | - Xiaodan Qin
- Departments of Pharmacology and Medicine, The Cancer Research Center, Section of Hematology and Medical Oncology, Boston University School of Medicine, Boston, MA, USA
| | - Fabrice J.F. Laroche
- Departments of Pharmacology and Medicine, The Cancer Research Center, Section of Hematology and Medical Oncology, Boston University School of Medicine, Boston, MA, USA
| | - Shajesh Palantavida
- Department of Mechanical Engineering, Tufts University, Medford, MA 02155, USA
| | - Maxim Dokukin
- Department of Mechanical Engineering, Tufts University, Medford, MA 02155, USA
| | - Hui Feng
- Departments of Pharmacology and Medicine, The Cancer Research Center, Section of Hematology and Medical Oncology, Boston University School of Medicine, Boston, MA, USA
| | - Igor Sokolov
- Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
- Department of Mechanical Engineering, Tufts University, Medford, MA 02155, USA
- Department of Physics, Tufts University, Medford, MA 02155, USA
| |
Collapse
|
|
43
|
Phthalocyanine-loaded nanostructured lipid carriers functionalized with folic acid for photodynamic therapy. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2019; 108:110462. [PMID: 31923986 DOI: 10.1016/j.msec.2019.110462] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Revised: 10/10/2019] [Accepted: 11/17/2019] [Indexed: 11/21/2022]
Abstract
Breast cancer is a serious public health problem that causes thousands of deaths annually. Chemotherapy continues to play a central role in the management of breast cancer but is associated with extreme off-target toxicity. Therefore, treatments that directly target the tumor and display reduced susceptibility to resistance could improve the outcome and quality of life for patients suffering from this disease. Photodynamic therapy is a targeted treatment based on the use of light to activate a photosensitizer (PS) that then interacts with molecular oxygen and other biochemical substrates to generate cytotoxic levels of Reactive Oxygen Species. Currently approved PS also tends to have poor aqueous solubility that can cause problems when delivered intravenously. In order to circumvent this limitation, in this manuscript, we evaluate the potential of a phthalocyanine-loaded nanostructured lipid carrier (NLC) functionalized with folic acid (FA). To prepare the FA labelled NLC, the polymer PF127 was first esterified with FA and emulsified with an oil phase containing polyoxyethylene 40 stearate, capric/caprylic acid triglycerides, ethoxylated hydrogenated castor oil 40 and the PS zinc phthalocyanine. The resulting PS loaded FA-NLC had a hydrodynamic diameter of 180 nm and were stable in suspension for >90 days. Interestingly, the amount of singlet oxygen generated upon light activation for the PS loaded FA-NLC was substantially higher than the free PS, yet at a lower PS concentration. The PS was released from the NLC in a sustained manner with 4.13 ± 0.58% and 27.7 ± 3.16% after 30 min and 7 days, respectively. Finally, cytotoxicity assays showed that NLC in the concentrations of 09.1 μM of PS present non-toxic with >80 ± 6.8% viable and after 90 s of the light-exposed the results show a statistically significant decrease in cell viability (57 ± 4%). The results obtained allow us to conclude that the functionalized NLC incorporated with PS associated with the PDT technique have characteristics that make them potential candidates for the alternative treatment of breast cancer.
Collapse
|
|
44
|
Synthesis and engineering of mesoporous ZnO@HAP heterostructure as a pH-sensitive nano-photosensitizer for chemo-photodynamic therapy of malignant tumor cells. J Drug Deliv Sci Technol 2019. [DOI: 10.1016/j.jddst.2019.101200] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
|
|
45
|
Heggannavar GB, Vijeth S, Kariduraganavar MY. Development of dual drug loaded PLGA based mesoporous silica nanoparticles and their conjugation with Angiopep-2 to treat glioma. J Drug Deliv Sci Technol 2019. [DOI: 10.1016/j.jddst.2019.101157] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
|
|
46
|
Hiremath CG, Heggnnavar GB, Kariduraganavar MY, Hiremath MB. Co-delivery of paclitaxel and curcumin to foliate positive cancer cells using Pluronic-coated iron oxide nanoparticles. Prog Biomater 2019; 8:155-168. [PMID: 31197663 PMCID: PMC6825627 DOI: 10.1007/s40204-019-0118-5] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 06/06/2019] [Indexed: 12/28/2022] Open
Abstract
Active targeting of folic acid and passive targeting of magnetic nanoparticles to bring about co-delivery of hydrophobic chemotherapeutic agents were the focus of this work. Co-precipitation in alkaline environment was employed for synthesizing Fe3O4 nanoparticles and stabilized by oleic acid. Aqueous dispersibility of oleic acid coated nanoparticles was brought about by folic acid modified Pluronic F127 and Pluronic F127 mixture. Folic acid is used as a targeting agent which was joined to Pluronic F127 via diethylene glycol bis(3-aminopropyl) ether spacer. The nanocomposite was used to delivery hydrophobic anticancer drugs, paclitaxel, and curcumin. Successful modification at each step was confirmed by FTIR and NMR. Quantitative analysis of attached folic acid indicated a total of 84.34% amount of conjugation. Nanoparticles characterization revealed the hydrodynamic size of and nanocomposite to be 94.2 nm nanometres. Furthermore, transmission electron micrograph reveals the size of the nanoparticle to be 12.5 nm hence also shows the superparamagnetic activity. Drug encapsulation efficiency of 34.7% and 59.5% was noted for paclitaxel and curcumin, respectively. Cytotoxic property of drug-loaded nanocomposites was increased in case of folic acid functionalized nanoparticles and further increased in the presence of an external magnetic field. Cellular uptake increased in the folic acid conjugated sample. Further many folds in the presence of an external magnetic field.
Collapse
Affiliation(s)
- Chinmay G Hiremath
- Department of Biotechnology and Microbiology, Karnatak University, Pavate Nagar, Dharwad, Karnataka, 580003, India
| | - Geetha B Heggnnavar
- Department of Chemistry, Karnatak University, Dharwad, Karnataka, 580003, India
| | | | - Murigendra B Hiremath
- Department of Biotechnology and Microbiology, Karnatak University, Pavate Nagar, Dharwad, Karnataka, 580003, India.
| |
Collapse
|
|
47
|
Samiei Foroushani M, Niroumand N, Karimi Shervedani R, Yaghoobi F, Kefayat A, Torabi M. A theranostic system based on nanocomposites of manganese oxide nanoparticles and a pH sensitive polymer: Preparation, and physicochemical characterization. Bioelectrochemistry 2019; 130:107347. [PMID: 31437809 DOI: 10.1016/j.bioelechem.2019.107347] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2019] [Revised: 08/04/2019] [Accepted: 08/05/2019] [Indexed: 01/17/2023]
Abstract
A multifunctional nanocomposite theranostic system is constructed of manganese oxide (Mn3O4) nanoparticles (NPs), as a tumor diagnostic agent, in conjunction with polyacrylic acid (PAA), as a pH-sensitive drug delivery agent, and methotrexate (MTX), as a model of targeting agent and anticancer drug. Physicochemical characteristics of the Mn3O4@PAA/MTX system is studied in detail by several techniques, including X-ray and Auger photoelectron spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, field-emission scanning electron microscopy, transmission electron microscopy, and electrochemical methods. The system performance is studied based on (i) in-vitro MRI measurements to support efficiency of the Mn3O4@PAA NPs as a diagnostic agent, (ii) drug release performance of the Mn3O4@PAA/MTX NPs at pHs of 5.4 and 7.4 through in-vitro method to evaluate application of the NPs as pH-sensitive nanocarriers for MTX, and (iii) impedance spectroscopy measurements to show Mn3O4@PAA/MTX NPs affinity for capturing of cancer cells. The results show that (i) Mn3O4@PAA NPs can be used as a contrast agent in MRI measurements (r1 ≅ 6.5 mM-1 s-1), (ii) the MTX, loaded on Mn3O4@PAA NPs, is released faster and more efficient at pH 5.4 than 7.4, and (iii) the GC-Mn3O4@PAA/MTX electrode system captures the 4T1 cells 3.32 times larger than L929 cells.
Collapse
Affiliation(s)
| | - Nazanin Niroumand
- Department of Chemistry, University of Isfahan, Isfahan 81746-73441, Iran
| | | | - Fatemeh Yaghoobi
- Department of Chemistry, University of Isfahan, Isfahan 81746-73441, Iran
| | - Amirhosein Kefayat
- Department of Oncology, Cancer Prevention Research Center, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
| | - Mostafa Torabi
- Department of Chemistry, University of Isfahan, Isfahan 81746-73441, Iran
| |
Collapse
|
|
48
|
Luiz MT, Abriata JP, Raspantini GL, Tofani LB, Fumagalli F, de Melo SMG, Emery FDS, Swiech K, Marcato PD, Lee R, Marchetti JM. In vitro evaluation of folate-modified PLGA nanoparticles containing paclitaxel for ovarian cancer therapy. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2019; 105:110038. [PMID: 31546359 DOI: 10.1016/j.msec.2019.110038] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Revised: 07/22/2019] [Accepted: 07/30/2019] [Indexed: 12/18/2022]
Abstract
Ovarian cancer is the most lethal gynecological cancer of female reproductive system. In order to improve the survival rate, some modifications on nanoparticles surfaces have been investigated to promote active targeting of drugs into tumor microenvironment. The aim of this study was the development and characterization of folate-modified (PN-PCX-FA) and unmodified PLGA nanoparticles (PN-PCX) containing paclitaxel for ovarian cancer treatment. Nanocarriers were produced using nanoprecipitation technique and characterized by mean particle diameter (MPD), polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), DSC, FTIR, in vitro cytotoxicity and cellular uptake. PN-PCX and PN-PCX-FA showed MPD < 150 nm and PDI < 0.2 with high EE (about 90%). Cytotoxicity assays in SKOV-3 cells demonstrated the ability of both formulations to cause cellular damage. PCX encapsulated in PN-PCX-FA at 1 nM showed higher cytotoxicity than PN-PCX. Folate-modified nanoparticles showed a 3.6-fold higher cellular uptake than unmodified nanoparticles. PN-PCX-FA is a promising system to improve safety and efficacy of ovarian cancer treatment. Further in vivo studies are necessary to prove PN-PCX-FA potential.
Collapse
Affiliation(s)
- Marcela Tavares Luiz
- School of Pharmaceutical Science of Ribeirão Preto, University of São Paulo, Avenida do café s/n, 14040-903 Ribeirão Preto, SP, Brazil
| | - Juliana Palma Abriata
- School of Pharmaceutical Science of Ribeirão Preto, University of São Paulo, Avenida do café s/n, 14040-903 Ribeirão Preto, SP, Brazil
| | - Giovanni Loureiro Raspantini
- School of Pharmaceutical Science of Ribeirão Preto, University of São Paulo, Avenida do café s/n, 14040-903 Ribeirão Preto, SP, Brazil
| | - Larissa Bueno Tofani
- School of Pharmaceutical Science of Ribeirão Preto, University of São Paulo, Avenida do café s/n, 14040-903 Ribeirão Preto, SP, Brazil
| | - Fernando Fumagalli
- School of Pharmaceutical Science of Ribeirão Preto, University of São Paulo, Avenida do café s/n, 14040-903 Ribeirão Preto, SP, Brazil
| | - Shaiani Maria Gil de Melo
- School of Pharmaceutical Science of Ribeirão Preto, University of São Paulo, Avenida do café s/n, 14040-903 Ribeirão Preto, SP, Brazil
| | - Flavio da Silva Emery
- School of Pharmaceutical Science of Ribeirão Preto, University of São Paulo, Avenida do café s/n, 14040-903 Ribeirão Preto, SP, Brazil
| | - Kamilla Swiech
- School of Pharmaceutical Science of Ribeirão Preto, University of São Paulo, Avenida do café s/n, 14040-903 Ribeirão Preto, SP, Brazil
| | - Priscyla Daniely Marcato
- School of Pharmaceutical Science of Ribeirão Preto, University of São Paulo, Avenida do café s/n, 14040-903 Ribeirão Preto, SP, Brazil
| | - Robert Lee
- Division of Pharmaceutics and Pharmaceutical Chemistry, Ohio State University, Columbus, OH, USA
| | - Juliana Maldonado Marchetti
- School of Pharmaceutical Science of Ribeirão Preto, University of São Paulo, Avenida do café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
| |
Collapse
|
|
49
|
Qindeel M, Ahmed N, Khan GM, Rehman AU. Ligand decorated chitosan as an advanced nanocarrier for targeted delivery: a critical review. Nanomedicine (Lond) 2019; 14:1623-1642. [PMID: 31166147 DOI: 10.2217/nnm-2018-0490] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Nontargeted delivery systems present nonspecific delivery, low transfection efficiency and high toxicity. Ligand-conjugated chitosan (CS) nanocarriers have emerged as an outstanding option for achieving active delivery specifically and preferentially to the target sites by exploiting receptors mediated endocytosis. Mannosylated CS nanocarriers have brought tremendous breakthrough in gene therapy and have proven to be an excellent choice for treatment of infectious and inflammatory diseases. Similarly, folate and antibodies-conjugated CS play a significant role in diagnosis and treatment of various cancers. Current evidences obviously propose ligand-decorated CS as an attractive option for diagnosis and treatment of dreadful conditions. In order to bring huge revolution in the field of targeted delivery, challenges associated with these nanocarriers needs to be addressed.
Collapse
Affiliation(s)
- Maimoona Qindeel
- Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Naveed Ahmed
- Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Gul Majid Khan
- Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Asim Ur Rehman
- Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan
| |
Collapse
|
|
50
|
Das B, Girigoswami A, Dutta A, Pal P, Dutta J, Dadhich P, Srivas PK, Dhara S. Carbon Nanodots Doped Super-paramagnetic Iron Oxide Nanoparticles for Multimodal Bioimaging and Osteochondral Tissue Regeneration via External Magnetic Actuation. ACS Biomater Sci Eng 2019; 5:3549-3560. [PMID: 33405737 DOI: 10.1021/acsbiomaterials.9b00571] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Super-paramagnetic iron oxide nanoparticles (SPIONs) have multiple theranostics applications such as T2 contrast agent in magnetic resonance imaging (MRI) and electromagnetic manipulations in biomedical devices, sensors, and regenerative medicines. However, SPIONs suffer from the limitation of free radical generation, and this has a certain limitation in its applicability in tissue imaging and regeneration applications. In the current study, we developed a simple hydrothermal method to prepare carbon quantum dots (CD) doped SPIONs (FeCD) from easily available precursors. The nanoparticles are observed to be cytocompatible, hemocompatible, and capable of scavenging free radicals in vitro. They also have been observed to be useful for bimodal imaging (fluorescence and MRI). Further, 3D printed gelatin-FeCD nanocomposite nanoparticles were prepared and used for tissue engineering using static magnetic actuation. Wharton's jelly derived mesenchymal stem cells (MSCs) were cultured on them with magnetic actuation and implanted at the subcutaneous region. The tissues obtained have shown features of both osteogenic and chondrogenic differentiation of the stem cells in vivo. In vitro, PCR studies show MSCs express gene expression of both bone and cartilage-specific markers, suggesting FeCDs under magnetic actuation can lead MSCs to go through differentiating into an endochondral ossification route.
Collapse
Affiliation(s)
- Bodhisatwa Das
- School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302, India
| | - Agnishwar Girigoswami
- Faculty of Allied Health Sciences, Chettinad Hospital & Research Institute (CHRI), Chettinad Academy of Research & Education (CARE), Kelambakkam, Chennai, Tamil Nadu 603103, India
| | - Abir Dutta
- Advanced Technology Development Centre Indian Institute of Technology Kharagpur Kharagpur, West Bengal 721302, India
| | - Pallabi Pal
- School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302, India
| | - Joy Dutta
- School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302, India
| | - Prabhash Dadhich
- School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302, India
| | - Pavan Kumar Srivas
- School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302, India
| | - Santanu Dhara
- School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302, India
| |
Collapse
|