Yang Yanfang, Xie Xiangyang, Xu Xueqing, Xia Xuejun, Wang Hongliang, Li Lin, Dong Wujun, Ma Panpan, Yang Yang, Liu Yuling, Mei Xingguo
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; State Key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Department of Pharmacy, Wuhan General Hospital of Guangzhou Command, Wuhan 430070, China.
Colloids Surf B Biointerfaces. 2016 Oct 1;146:607-15. doi: 10.1016/j.colsurfb.2016.07.002. Epub 2016 Jul 2.
Due to the absence of effective in vivo delivery systems, the employment of small interfering RNA (siRNA) in the clinic has been hindered. Here, we describe a novel siRNA targeting system that combines features of biological (cell-permeable peptides, CPPs) and physical (magnetic) siRNA targeting for use in magnetic hyperthermia-triggered release. A siRNA-CPPs conjugate (siRNA-CPPs) was loaded into thermal and magnetic dual-responsive liposomes (TML) (siRNA-CPPs/TML), and in vitro siRNA-CPPs thermosensitive release activity, targeted cellular uptake, gene silencing efficiency, in vivo targeted delivery and in vivo antitumor activity were determined. The results demonstrated that siRNA-CPPs/TML exhibited good physicochemical properties, effective cellular uptake, endosomal escape and a significant gene silencing efficiency in MCF-7 cells in vitro. Additionally, in the in vivo study, siRNA-CPPs/TML under an alternating current (AC) magnetic field displayed a superior in vivo targeted delivery efficacy, antitumor efficacy and gene silencing efficiency in a MCF-7 xenograft murine model. In conclusion, the application of siRNA-CPPs/TML under an AC magnetic field represents a new strategy for the selective and efficient delivery of siRNA.
由于缺乏有效的体内递送系统，小干扰RNA（siRNA）在临床上的应用受到了阻碍。在此，我们描述了一种新型的siRNA靶向系统，该系统结合了生物（细胞穿透肽，CPPs）和物理（磁性）siRNA靶向的特性，用于磁热疗触发释放。将siRNA-CPPs缀合物（siRNA-CPPs）负载到热和磁双响应脂质体（TML）中（siRNA-CPPs/TML），并测定了体外siRNA-CPPs的热敏释放活性、靶向细胞摄取、基因沉默效率、体内靶向递送和体内抗肿瘤活性。结果表明，siRNA-CPPs/TML在体外对MCF-7细胞表现出良好的物理化学性质、有效的细胞摄取、内体逃逸和显著的基因沉默效率。此外，在体内研究中，在交变电流（AC）磁场下，siRNA-CPPs/TML在MCF-7异种移植小鼠模型中显示出优异的体内靶向递送效果、抗肿瘤效果和基因沉默效率。总之，在AC磁场下应用siRNA-CPPs/TML代表了一种选择性和高效递送siRNA的新策略。
