Chen Zhenzhen, Zhu Pingping, Zhang Yushun, Liu Yating, He Yuling, Zhang Lifen, Gao Yanfeng
School of Life Sciences, Zhengzhou University , Zhengzhou 450001, China.
School of Life Sciences, University of Science and Technology of China , Hefei, Anhui 230027, China.
Mol Pharm. 2016 Aug 1;13(8):2749-59. doi: 10.1021/acs.molpharmaceut.6b00352. Epub 2016 Jul 5.
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.
癌症干细胞（CSCs）通过高表达ABCG2导致癌症耐药，ABCG2将内化的化疗药物泵出以逃避药物诱导的细胞毒性。在此，我们建立了一种功能化介孔二氧化硅纳米颗粒（MSN）系统，以协同递送shABCG2和阿霉素（Dox）。凭借出色的细胞摄取和内体逃逸能力，双递送载体将shABCG2和Dox有效地内化到CSCs中。ABCG2的缺失增加了细胞内和细胞核内Dox的富集，引发了强烈的Dox诱导的细胞死亡，并损害了CSCs的自我更新能力。此外，纳米颗粒在体内能有效消除肿瘤并减少CSCs引发的肿瘤，且副作用可忽略不计。我们的研究结果表明，精心设计的传统化疗药物递送系统在CSC治疗方面具有广阔前景。
