Cancer-targeted MDR-1 siRNA delivery using self-cross-linked glycol chitosan nanoparticles to overcome drug resistance
作者： Ji Young Yhee , Seungyong Song , So Jin Lee , Sung-Gurl Park , Ki-Suk Kim
DOI: 10.1016/J.JCONREL.2014.11.019
关键词: Chitosan 、 Pharmacology 、 Small interfering RNA 、 Gene silencing 、 Cancer cell 、 Combination therapy 、 Cancer 、 In vivo 、 Chemistry 、 Doxorubicin
摘要: P-glycoprotein (Pgp) mediated multi-drug resistance (MDR) is a major cause of failure in chemotherapy. In this study, small interfering RNA (siRNA) for Pgp down-regulation was delivered to tumors overcome MDR cancer. To achieve an efficient siRNA delivery vivo, self-polymerized 5'-end thiol-modified (poly-siRNA) incorporated tumor targeting glycol chitosan nanoparticles. Pgp-targeted poly-siRNA (psi-Pgp) and thiolated polymers (tGC) formed stable nanoparticles (psi-Pgp-tGC NPs), the resulting protected molecules from enzymatic degradation. The psi-Pgp-tGC NPs could release functional after cellular delivery, they were able facilitate Adriamycin-resistant breast cancer cells (MCF-7/ADR). After intravenous administration, accumulated MCF-7/ADR down-regulated P-gp expression sensitize cells. Consequently, chemo-siRNA combination therapy significantly inhibited growth without systemic toxicity. These showed great potential as supplementary therapeutic agent drug-resistant
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