Issue 1, 2018

Co-delivery of PLK1-specific shRNA and doxorubicin via core-crosslinked pH-sensitive and redox ultra-sensitive micelles for glioma therapy

Abstract

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.

Graphical abstract: Co-delivery of PLK1-specific shRNA and doxorubicin via core-crosslinked pH-sensitive and redox ultra-sensitive micelles for glioma therapy

Supplementary files

Article information

Article type
Paper
Submitted
12 Aug 2017
Accepted
29 Nov 2017
First published
29 Nov 2017

J. Mater. Chem. B, 2018,6, 112-124

Co-delivery of PLK1-specific shRNA and doxorubicin via core-crosslinked pH-sensitive and redox ultra-sensitive micelles for glioma therapy

P. Wang, N. Yu, Y. Wang, H. Sun, Z. Yang and S. Zhou, J. Mater. Chem. B, 2018, 6, 112 DOI: 10.1039/C7TB02160G

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