Se/Ru-Decorated Porous Metal–Organic Framework Nanoparticles for The Delivery of Pooled siRNAs to Reversing Multidrug Resistance in Taxol-Resistant Breast Cancer Cells

• DOI: 10.1021/acsami.6b12792
• Publication Date: 2017-02-13T15:56:36Z
• Authors: Qingchang Chen; Meng Xu; Wenjing Zheng; Taoyuan Xu; Hong Deng; Jie Liu
• Keywords: Paclitaxel; Mice, Nude; Breast Neoplasms; 02 engineering and technology; Drug Resistance, Multiple; Ruthenium; 3. Good health; Mice; Phosphatidylinositol 3-Kinases; Selenium; Drug Resistance, Neoplasm; Cell Line, Tumor; Animals; Humans; Nanoparticles; RNA, Small Interfering; 0210 nano-technology; Metal-Organic Frameworks

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 interfere with microtubule (MT) dynamics in MCF-7/T (Taxol-resistance) cell. The existence coordinatively unsaturated sites can strongly interact the electron-rich functional groups cysteine, which be regarded as linkage between MIL-101(Fe). Se@MIL-101 Ru@MIL-101 loaded MDR gene-silencing siRNAs via surface coordination significantly protection against nuclease degradation, increase siRNA cellular uptake, promote escape from endosomes/lysosome silence cell, resulting enhanced cytotoxicity through induction apoptosis signaling pathways phosphorylation p53, MAPK, PI3K/Akt dynamic instability MTs disrupting normal mitotic spindle formation. Furthermore, vivo investigation on nude mice bearing cancer xenografts confirmed that Se@MIL-101-(P+V)siRNA therapeutic decrease systemic toxicity vivo.