Journal
JOURNAL OF MATERIALS CHEMISTRY B
Volume 6, Issue 1, Pages 112-124Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c7tb02160g
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Funding
- National Natural Science Foundation of China [51373138, 21574105, 51725303]
- National Key Research and Development Program of China [2017YFB0702600, 2017YFB0702602]
- Sichuan Province Youth Science and Technology Innovation Team [2016TD0026]
- Fundamental Research Funds for the Central Universities [2682017ZT02]
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Anticancer drug delivery encounters many biological barriers, including mucosal barriers, nonspecific uptake and intracellular drug resistance. Consequently, efficient delivery of therapeutic agents with nanocarriers to the target cell and controlled intracellular release of encapsulated drugs are key to achieving high therapeutic efficiency. In this study, we develop a tumor microenvironment-sensitive polymer micelle system from a pH- and glutathione (GSH) dual-responsive copolymer with each repeating unit containing a disulfide bond. To prevent premature drug release within the blood circulation, the core region was chemically crosslinked via UV light irradiation. In tumor cells, the micelles are able to escape from the acidic lysosome into the cytoplasm via a prompt expansion due to the proton sponge effect''. Subsequently, ultra-sensitive redox responsiveness is realized since the abundant disulfide bonds of the micellar matrix can be cleaved by a high level of GSH, leading to a rapid intracellular release of encapsulated doxorubicin (DOX) and PLK1-specific shRNA. The antitumor activity in U87 glioma tumor bearing mice reveals that this novel system possesses a high therapeutic efficacy against solid tumors with negligible side effects on normal tissues. Therefore, this micellar nanoplatform has great potential in delivering drugs for enhanced glioma therapy.
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