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Actively targeted delivery of anticancer drug to tumor cells by redox-responsive star-shaped micelles
Abstract
In cancer therapy nanocargos based on star-shaped polymer exhibit unique features such as better stability, smaller size distribution and higher drug capacity in comparison to linear polymeric micelles. In this study, we developed a multifunctional star-shaped micellar system by combination of active targeting ability and redox-responsive behavior. The star-shaped micelles with good stability were self-assembled from four-arm poly(ε-caprolactone)-poly(ethylene glycol) copolymer. The redox-responsive behaviors of these micelles triggered by glutathione were evaluated from the changes of micellar size, morphology and molecular weight. In vitro drug release profiles exhibited that in a stimulated normal physiological environment, the redox-responsive star-shaped micelles could maintain good stability, whereas in a reducing and acid environment similar with that of tumor cells, the encapsulated agent was promptly released. In vitro cellular uptake and subcellular localization of these micelles were further studied with confocal laser scanning microscopy and flow cytometry against the human cervical cancer cell line HeLa. In vivo and ex vivo DOX fluorescence imaging displayed that these FA-functionalized star-shaped micelles possessed much better specificity to target solid tumor. Both the qualitative and quantitative results of the antitumor effect in 4T1 tumor-bearing BALB/c mice demonstrated that these redox-responsive star-shaped micelles have a high therapeutic efficiency to artificial solid tumor. Therefore, the multifunctional star-shaped micelles are a potential platform for targeted anticancer drug delivery.
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“The coupling of hydrophilic terminal groups with folate units for active targeting showed high stability and exhibited sustained release.247”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [247]
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Metadata
- Authors
- Shi, C., Guo, X., Qu, Q., Tang, Z., Wang, Y., & Zhou, S.
- Affiliations
- Southwest Jiaotong University (CN)
- Corresponding author
- Zhou, Shaobing
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 35
- Issue
- 30
- Pages
- 8711-8722
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2030897628
- Cited by
- 189
- References
- 45
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 10 · 2023: 10 · 2022: 14 · 2021: 20 · 2020: 22 · 2019: 15 · 2018: 29 · 2017: 19 · 2016: 23 · 2015: 20 · 2014: 3
- FWCI
- 8.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Basic Research Program of China (2012CB933600)
- National Natural Science Foundation of China (51173150, 51373138)
- Research Fund for the Doctoral Program of Higher Education of China (20120184110029)
- Construction Program for Innovative Research Team of University in Sichuan Province (14TD0050)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- redox-responsive drug delivery, polymeric micelles, glutathione-responsive release, folic acid targeting, doxorubicin, anticancer drug delivery, HeLa cells, 4T1 breast cancer, fluorescence imaging, antitumor efficacy
- MeSH terms
- Animals, Antineoplastic Agents, Doxorubicin, Female, Flow Cytometry, Folic Acid, Glutathione, Humans, Mice, Inbred BALB C, Mice, Nude, Micelles, Neoplasms, Oxidation-Reduction, Particle Size, Polyesters, Tissue Distribution, Drug Delivery Systems, Cell Death, In Situ Nick-End Labeling, Cell Line, Tumor, Proton Magnetic Resonance Spectroscopy
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