Cylindrical polymer brushes-anisotropic unimolecular micelle drug delivery system for enhancing the effectiveness of chemotherapy
| Autor: | Mengyun Liang, Shuang Bai, Peng Xue, Die Jia, Zhigang Xu, Xianbin Ma, Yuejun Kang |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Materials science
Cancer therapy QH301-705.5 Reduction-responsive 0206 medical engineering Biomedical Engineering 02 engineering and technology Methacrylate Micelle Article Biomaterials chemistry.chemical_compound Hydrophily Biology (General) Prodrug Materials of engineering and construction. Mechanics of materials chemistry.chemical_classification Atom-transfer radical-polymerization Polymer 021001 nanoscience & nanotechnology 020601 biomedical engineering Monomer chemistry Chemical engineering Drug delivery TA401-492 Cylindrical polymer brushes 0210 nano-technology Ethylene glycol Unimolecular micelles Biotechnology |
| Zdroj: | Bioactive Materials, Vol 6, Iss 9, Pp 2894-2904 (2021) Bioactive Materials |
| Popis: | Polymer systems can be designed into different structures and morphologies according to their physical and chemical performance requirements, and are considered as one of the most promising controlled delivery systems that can effectively improve the cancer therapeutic index. However, the majority of the polymer delivery systems are designed to be simple spherical nanostructures. To explore morphology/size-oriented delivery performance optimization, here, we synthesized three novel cylindrical polymer brushes (CPBs) by atom transfer radical polymerization (ATRP), which were cellulose-g-(CPT-b-OEGMA) (CCO) with different lengths (~86, ~40, and ~21 nm). The CPBs are composed of bio-degradable cellulose as the carrier, poly(ethylene glycol) methyl ether methacrylate (OEGMA) as hydrophily block, and glutathione (GSH)-responsive hydrophobic camptothecin (CPT) monomer as loaded anticancer drug. By controlling the chain length of the initiator, three kinds of polymeric prodrugs with different lengths (CCO-1, CCO-2, and CCO-3) could be self-organized into unimolecular micelles in water. We carried out comparative studies of three polymers, whose results verified that the shorter CPBs exhibited higher drug release efficiency, more cellular uptake, and enhanced tumor permeability, accompanied by shortened blood circulation time and lower tumor accumulation. As evidenced by in vivo experiments, the shorter CPBs exhibited higher anti-tumor efficiency, revealing that the size advantage has a higher priority than the anisotropic structure advantage. This provided vital information as to design an anisotropic polymer-based drug delivery system for cancer therapy. Graphical abstract Image 1 Highlights • Reduction-responsive cylindrical polymer brushes (CPBs) could reshape the tumor microenvironment to reinforce chemotherapy. • Three cellulose prodrugs-based CPBs with different lengths could form into unimolecular micelles in water. • Longer CPBs exhibited prolonged blood circulation time and higher tumor accumulation. • The CPBs showed an enhanced chemotherapy with real-time NIRF imaging. |
| Databáze: | OpenAIRE |
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