Enhanced Sensitivity of Cancer Stem Cells to Chemotherapy Using Functionalized Mesoporous Silica Nanoparticles

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• 作者：Zhenzhen Chen ; Pingping Zhu ; Yushun Zhang ; Yating Liu ; Yuling He ; Lifen Zhang ; Yanfeng Gao
• 刊名：Molecular Pharmaceutics
• 出版年：2016
• 出版时间：August 1, 2016
• 年：2016
• 卷：13
• 期：8
• 页码：2749-2759
• 全文大小：759K
• 年卷期：0
• ISSN：1543-8392

文摘

Cancer stem cells (CSCs) are responsible for cancer drug resistance with high expression of ABCG2, which pumps the internalized chemotherapeutic out to escape drug-induced cytotoxicity. Here, we established a functionalized mesoporous silica nanoparticle (MSN) system to deliver shABCG2 and doxorubicin (Dox) synergistically. With excellent cell uptake and endosomal escape capacities, the dual-delivery carriers internalized shABCG2 and Dox into CSCs efficiently. ABCG2 depletion increased intracellular and intranuclear Dox enrichment, drove vigorous Dox-induced cell death, and impaired the self-renewal of CSCs. Additionally, the nanoparticles eliminated tumors efficiently and reduced tumor initiation by CSCs in vivo, with negligible side effects. Our findings suggest that well-designed delivery systems for conventional chemotherapeutic agents are promising for CSC therapy.