用于肿瘤治疗的小干扰RNA高效递送载体的设计进展

Progress in Design of Efficient siRNA Vectors for Cancer Therapy

小干扰RNA(siRNA)能特异性地沉默靶细胞中异常表达的基因,在癌症的治疗中具有广阔的应用前景。但是siRNA的体内稳定性差,易被核酸酶降解,易被肾清除,而且siRNA是负电性的亲水大分子,难以跨过细胞膜进入胞质,这些特点限制了siRNA的临床应用。而通过载体将siRNA递送到靶细胞胞质中,是推动siRNA临床应用的前提。但siRNA载体在体内递送siRNA时仍面临多重生理病理屏障,包括血液屏障、组织屏障和细胞屏障。因此,为了实现siRNA的高效递送,研究者们从提高载体的血液稳定性、体内靶向性、肿瘤深层穿透、细胞摄取、内涵体逃逸以及药物释放等多方面进行了高效siRNA递送载体的设计。基于此,文章综述了近年来用于肿瘤治疗的siRNA高效递送载体的设计进展,期望能为siRNA载体的设计提供参考,推动siRNA在肿瘤治疗中的应用。

Small interference RNA（siRNA） can specifically silence abnormally expressed genes in target cells,which has a promising potential in the treatment of cancer. However,siRNA has great limitations in clinical applications which can be briefly summarized into following aspects. Firstly,siRNA is easily degraded by nucleases in plasma as well as metabolized by liver and rapidly cleared by kidney. As a result,the plasma half-life is relatively short. Secondly,siRNA is highly hydrophilic and negatively charged,which is inferior for it to penetrate through cell membrane to reach cytoplasm. Therefore,siRNA needs to be delivered to the target cells through the suitable vector in order to silence the target genes. The siRNA vector needs to overcome the blood barrier,tissue barrier and cell barrier to reach the site of action from the site of administration. In order to achieve efficient delivery of siRNA,researchers have designed efficient siRNA delivery vectors for improving blood stability,enhancing in vivo targeting,enhancing tumor tissue penetration,increasing tumor cellular uptake,facilitating endosomal escapeand promoting drug release. This article reviews the progress in the design of vectors for siRNA delivery and it is expected to provide a guide line for the rational design of siRNA vectors and to promote the clinical use of siRNA in cancer treatment.