期刊
BIOMATERIALS
卷 121, 期 -, 页码 41-54出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.01.002
关键词
Visible light; Crosslinking; Diselenide bonds; Redox responsiveness; Combination chemotherapy
资金
- National Natural Scientific Foundation of China (NSFC) [81630046]
- NSFC [61361160414, 21674040, 51403042, 81371646]
- Natural Science Foundation for Distinguished Young Scholars of Guangdong Province [2016A030306013]
- Guangdong Program for Support of Top-notch Young Professionals [2015TQ01R604]
- Natural Science Foundation of Guangdong Province [2014A030310310]
- Scientific Research Projects of Guangzhou [201607010328]
Undesired physiological instability of nanocarriers and premature drug leakage during blood circulation result in compromised therapeutic efficacy and severe side effects, which have significantly impeded the development of nanomedicine. Facile crosslinking of drug-loaded nanocarriers while keeping the potency of site-specific degradation and drug release has emerged as a viable strategy to overcome these drawbacks. Additionally, combination therapy has already shown advantages in inhibiting advanced tumors and life extension than single drug therapy. Herein, three kinds of diselenide-rich polymers were fabricated with distinct hydrophobic side chains. The component effect was interrogated to screen out PEG-b-PBSe diblock copolymer due to its favorable self-assembly controllability and high drug loading of camptothecin (CPT) and doxorubicin (DOX) that had synergistic antitumor property. Facile visible light induced diselenide metathesis and regeneration was employed to crosslink nanocarriers for the first time. The dual drug-loaded crosslinked micelles (CPT/DOX-CCM) were stable in physiological conditions with minimal drug leakage, possessing extended blood circulation, whereas hand-in-hand dual drug release was significantly accelerated in tumor's redox microenvironments. In vitro cytotoxicity evaluation and in vivo tumor suppression with low dosage drugs further demonstrated the favorable potency of the redox-responsive nanoplatform in tumor combination chemotherapy. (C) 2017 Elsevier Ltd. All rights reserved.
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