Enhanced Sensitivity of Cancer Stem Cells to Chemotherapy Using Functionalized Mesoporous Silica Nanoparticles
Enhanced Sensitivity of Cancer Stem Cells to Chemotherapy Using Functionalized Mesoporous Silica Nanoparticles
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使用功能化介孔二氧化硅纳米颗粒增强癌症干细胞对化疗的敏感性
DOI：
10.1021/acs.molpharmaceut.6b00352
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发表时间：
2016-08-01
影响因子：
4.9
通讯作者：
Gao, Yanfeng
中科院分区：
文献类型：
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作者：
Chen, Zhenzhen;Zhu, Pingping;Gao, Yanfeng
肿瘤干细胞(CSCs)高表达ABCG2，将内化的化疗药物排出体外，逃避药物诱导的细胞毒作用，导致肿瘤耐药。在这里，我们建立了一种功能化的介孔二氧化硅纳米颗粒(MSN)系统来协同传递shABCG2和阿霉素(Dox)。双重递送载体具有良好的细胞摄取和内体逃逸能力，能有效地将shABCG2和Dox内化到CSCs中。ABCG2缺失增加了细胞内和核内Dox的聚集，促使Dox诱导的细胞死亡，并损害了CSCs的自我更新。此外，纳米粒有效地消除了肿瘤，减少了肿瘤干细胞在体内的启动，副作用可以忽略不计。我们的发现表明，为传统化疗药物设计良好的给药系统在CSC治疗中是有前景的。
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.