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

      1 , 2 , 2 , 3 , 4 , 1 , 2 , 1 , 2 , 2 , 4 , 5 , 1 , 2 , 5

      ACS Nano

      American Chemical Society (ACS)

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          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 drugs. 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 the drug-sensitive MCF-7 counterpart. It was found that the combination of T-type Ca2+ channel siRNA and DOX had a similar effect on MCF-7 and MCF-7/ADR in the knockdown of overexpressed T-type Ca2+ channels 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 biological target for drug/gene delivery enhanced cancer therapy with nanoformulations.

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          Author and article information

          Journal
          ACS Nano
          ACS Nano
          American Chemical Society (ACS)
          1936-0851
          1936-086X
          December 21 2018
          December 21 2018
          Affiliations
          [1 ]Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 100083, P. R. China
          [2 ]School of Nanoscience and Technology, University of Chinese Academy of Sciences, Beijing 100049, P. R. China
          [3 ]CAS Key Laboratory of Bio-Inspired Materials and Interfacial Science, CAS Center for Excellence in Nanoscience, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China
          [4 ]Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, P. R. China
          [5 ]Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience, Beijing 100190, P. R. China
          Article
          10.1021/acsnano.8b05639
          30566319
          © 2018
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