title: Se/Ru-Decorated Porous Metal-Organic Framework Nanoparticles for The Delivery of Pooled siRNAs to Reversing Multidrug Resistance in Taxol-Resistant Breast Cancer Cells.
abstract: 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.
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Qingchang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Taoyuan
authors.initials: T
authors.lastname: Xu
authors.affiliation: Key Laboratory of Electrochemical Technology on Energy Storage and Power Generation of Guangdong Higher Education Institutes, South China Normal University , Guangzhou 510006, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Deng
authors.affiliation: Department of Chemistry, Jinan University , Guangzhou 510632, China.
authors.forename: Jie
authors.identifier: http://orcid.org/0000-0003-2237-9309
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000073396:Metal-Organic Frameworks; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D017239:Paclitaxel; D019869:Phosphatidylinositol 3-Kinases; D034741:RNA, Small Interfering; D012428:Ruthenium; D012643:Selenium
chemical_list: D000073396:Metal-Organic Frameworks; D034741:RNA, Small Interfering; D012428:Ruthenium; D019869:Phosphatidylinositol 3-Kinases; D012643:Selenium; D017239:Paclitaxel
keywords: MOF surface modifications; multidrug resistance cancer therapy; selenium/ruthenium nanoparticle; siRNA delivery systems; tubulin polymerization