Regulation of Ca2+ Signaling for Drug-Resistant Breast Cancer Therapy with Mesoporous Silica Nanocapsules Encapsulated Doxorubicin/siRNA Cocktail.

Regulation of Ca2+ Signaling for Drug-Resistant Breast Cancer Therapy with Mesoporous Silica Nanocapsules Encapsulated Doxorubicin/siRNA Cocktail.

ACS Nano. 2018 Dec 19;:

Authors: Wang S, Liu X, Chen S, Liu Z, Zhang X, Liang XJ, Li L

Abstract
Multidrug resistance (MDR) is the key cause that accounts for the failure of clinical cancer chemotherapy. To address the problem, herein, we presented an alternative strategy to conquer drug-resistant breast cancer through the combinatorial delivery of Ca2+ channel siRNA with cytotoxic drug. Mesoporous silica nanocapsules (MSNCs) with mesoporous and hollow structure were fabricated for co-delivery of T-type Ca2+ channel siRNA and doxorubicin (DOX) with high drug loading efficiency. The DOX/siRNA co-loaded MSNCs showed a synergistic therapeutic effect on drug-resistant breast cancer cells MCF-7/ADR, while had only an additive effect on drug-sensitive MCF-7 counterpart. It was found that the combination of T-type Ca2+ channel siRNA and DOX had similar effect on MCF-7 and MCF-7/ADR in knockdown of overexpressed T-type Ca2+ channel and decrease in cytosolic Ca2+ concentration ([Ca2+]i), but it specifically induced G0/G1 phase cell-cycle arrest and intracellular drug accumulation enhancement in MCF-7/ADR. The in vitro and in vivo results demonstrated that the MSNCs with good biocompatibility had a high efficiency for conquering the drug-resistant breast cancer with the DOX/calcium channel siRNA cocktail co-delivery. It provides a new biological target for drug/gene delivery enhanced cancer therapy with nanoformulations.

PMID: 30566319 [PubMed - as supplied by publisher]

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