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Cell-penetrating poly(disulfide)s-based star polymer for simultaneous intracellular delivery of miRNAs and small molecule drugs

Abstract

MicroRNAs (miRNAs) are small regulatory noncoding RNAs that control a variety of biological processes. The regulation of many endogenous miRNAs is tightly associated with various diseases. Thus, the design of miRNAs delivery systems with minimal endolysosomal trapping, efficient delivery and controlled miRNAs release is urgently needed. Herein, we have developed a new star polymer which consists of a β-cyclodextrin (βCD) core and multiple cell-penetrating poly(disulfide)s (CPDs) arms. By subsequently loading the system with miRNAs and small molecule drugs, we have successfully proven that this novel drug delivery platform could efficiently enter mammalian cells (<2 h) without apparent endolysosomal trapping. The global Pearson’s R value was calculated to be 0.31 between our complex and endolysosome, which is far below the threshold of >0.5 required for correlation. In addition, the GSH-triggered degradation of CPD arms and subsquent intracellular release of miR-203 and CPT, as well as the combination therapeutic effects have been sucessfully demonstrated. In this way, we show this novel platform could be used in future to minimize potential cytotoxicity encountered by many existing cationic branched polymer systems in miRNAs delivery. Our results provide important starting points for using CPD-based polymers to design personalized delivery platform.

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Publication details

The article was received on 20 Apr 2017, accepted on 18 Jun 2017 and first published on 19 Jun 2017


Article type: Paper
DOI: 10.1039/C7PY00666G
Citation: Polym. Chem., 2017, Accepted Manuscript
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    Cell-penetrating poly(disulfide)s-based star polymer for simultaneous intracellular delivery of miRNAs and small molecule drugs

    W. Yang, C. Yu, C. Wu, S. Yao and S. Wu, Polym. Chem., 2017, Accepted Manuscript , DOI: 10.1039/C7PY00666G

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