基因沉默
小干扰RNA
材料科学
多重耐药
阿霉素
癌症研究
紫杉醇
细胞毒性
蛋白激酶B
癌细胞
纳米颗粒
细胞生物学
药物输送
体内
纳米载体
细胞培养
细胞凋亡
转染
生物
信号转导
体外
生物化学
基因
生物技术
抗生素
作者
Qingchang Chen,Meng Xu,Wenjing Zheng,Taoyuan Xu,Hong Deng,Jie Liu
标识
DOI:10.1021/acsami.6b12792
摘要
We report here a novel and personalized strategy of selenium/ruthenium nanoparticles modified metal organic frameworks MIL-101(Fe) for delivering pooled small interfering RNAs (siRNAs) to enhance therapy efficacy by silencing multidrug resistance (MDR) genes and interfere with microtubule (MT) dynamics in MCF-7/T (Taxol-resistance) cell. The existence of coordinatively unsaturated metal sites in MIL-101(Fe) can strongly interact with the electron-rich functional groups of cysteine, which can be regarded as the linkage between selenium/ruthenium nanoparticles and MIL-101(Fe). Se@MIL-101 and Ru@MIL-101 loaded with MDR gene-silencing siRNAs via surface coordination can significantly enhance protection of siRNAs against nuclease degradation, increase siRNA cellular uptake, and promote siRNA escape from endosomes/lysosome to silence MDR genes in MCF-7/T cell, resulting in enhanced cytotoxicity through the induction of apoptosis with the signaling pathways of phosphorylation of p53, MAPK, and PI3K/Akt and the dynamic instability of MTs and disrupting normal mitotic spindle formation. Furthermore, in vivo investigation of the nanoparticles on nude mice bearing MCF-7/T cancer xenografts confirmed that Se@MIL-101-(P+V)siRNA nanoparticles can significantly enhance cancer therapeutic efficacy and decrease systemic toxicity in vivo.
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