siRNA和miRNA疗法的基础以及乳腺癌中靶向纳米颗粒递送系统的综述。
Fundamentals of siRNA and miRNA therapeutics and a review of targeted nanoparticle delivery systems in breast cancer.
作者信息
Ahmadzada Tamkin, Reid Glen, McKenzie David R
机构信息
Sydney Medical School, The University of Sydney, Sydney, Australia.
Asbestos Diseases Research Institute (ADRI), Sydney, Australia.
出版信息
Biophys Rev. 2018 Feb;10(1):69-86. doi: 10.1007/s12551-017-0392-1. Epub 2018 Jan 11.
Abstract
Gene silencing via RNA interference (RNAi) is rapidly evolving as a personalized approach to cancer treatment. The effector molecules-small interfering RNAs (siRNAs) and microRNAs (miRNAs)-can be used to silence or "switch off" specific cancer genes. Currently, the main barrier to implementing siRNA- and miRNA-based therapies in clinical practice is the lack of an effective delivery system that can protect the RNA molecules from nuclease degradation, deliver to them to tumor tissue, and release them into the cytoplasm of the target cancer cells, all without inducing adverse effects. Here, we review the fundamentals of RNAi, cell membrane transport pathways, and factors that affect intracellular delivery. We discuss the advantages and disadvantages of the various types of nanoparticle delivery systems, with a focus on those that have been investigated in breast cancer in vivo.
摘要
通过RNA干扰（RNAi）实现的基因沉默正迅速发展成为一种个性化的癌症治疗方法。效应分子——小干扰RNA（siRNAs）和微小RNA（miRNAs）——可用于沉默或“关闭”特定的癌症基因。目前，在临床实践中实施基于siRNA和miRNA的疗法的主要障碍是缺乏一种有效的递送系统，该系统能够保护RNA分子不被核酸酶降解，将它们递送至肿瘤组织，并将它们释放到靶癌细胞的细胞质中，同时不会产生不良反应。在此，我们综述了RNAi的基本原理、细胞膜转运途径以及影响细胞内递送的因素。我们讨论了各种类型纳米颗粒递送系统的优缺点，重点关注那些已在乳腺癌体内研究中得到考察的系统。
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