Peptide-assembled siRNA nanomicelles confine MnOx-loaded silicages for synergistic chemical and gene-regulated cancer therapy  

作　　者：Jingjing Li Juanjuan Wei Yixuan Gao Qi Zhao Jianghui Sun Jin Ouyang Na Na 

机构地区：[1]Key Laboratory of Radiopharmaceuticals,Ministry of Education,College of Chemistry,Beijing Normal University,Beijing 100085,China

出　　处：《Chinese Chemical Letters》2023年第4期453-458,共6页中国化学快报（英文版）

基　　金：the financial support provided by the National Natural Science Foundation of China (NNSFC, No. 21874012);the National Key Research and Development Program of China (No.2019YFC1805600);the financial support provided by NNSFC (No. 21974010)。

摘　　要：Chemodynamic therapy(CDT) is a promising therapeutic approach for in situ cancer treatment, but it is still hindered by inefficient single-modality treatment and the weak targeted delivery of reagents into mitochondria(the main site of intracellular ROS production). Herein, to obtain a multimodal strategy,peptide-assembled si RNA nanomicelles were prepared to confine ultrasmall MnOxin small silica cages(silicages), which is convenient for synergistic chemical and gene-regulated cancer therapy. Given the free energy and versatility of small silicages, as well as the excellent Fenton-like activity of ultrasmall MnOx,MnOx-inside-loaded silicages(10 nm) were prepared for CDT delivery to mitochondria. Subsequently, to obtain a synergistic CDT and gene silencing treatment, the peptide-mediated assembly of si RNA and MnOx-loaded silicages were employed to obtain silicage@MnOx-si RNA nanomicelles(SMS NMs). After multiple modifications, sequential cancer cell-targeted delivery, GSH-controlled reagent release of si RNA and mitochondria-targeted delivery of MnOx-loaded silicages were successfully achieved. Finally, by both in vitro and in vivo experiments, SMS NMs were confirmed to be effective for synergistic chemical and gene-regulated cancer therapy. Our findings expand the applications of silicages and initiate the development of multimodal CDT.

关 键 词：Peptide-assembled siRNA nanomicelles MnOx-loaded silicages GSH-stimulated release Mitochondria-targeted delivery Cancer therap 

分 类 号：TQ127.2[化学工程—无机化工] R730.5[医药卫生—肿瘤]