Progress and perspective of inorganic nanoparticle-based siRNA delivery systems.
Progress and perspective of inorganic nanoparticle-based siRNA delivery systems.
复制标题
DOI：
10.1517/17425247.2016.1134486
复制
发表时间：
2016
影响因子：
6.6
通讯作者：
Rotello VM
中科院分区：
文献类型：
--
作者：
Jiang Y;Huo S;Hardie J;Liang XJ;Rotello VM
小干扰RNA（siRNA）是一种有效的方法，用于调节蛋白质的表达，甚至是“undruggable”的那些几乎不可能通过传统的小分子治疗靶向。递送至细胞，然后递送至胞质溶胶是实现siRNA的治疗潜力的主要要求。我们总结了最近的进展，在设计的无机纳米粒子的表面功能和物理化学性质的siRNA交付工程。具体而言，我们讨论了目前开发的主要方法，以加载siRNA到/到NP，NP表面化学工程增强细胞内siRNA的交付，内体逃逸，并有针对性地交付siRNA的疾病细胞和组织。在开发用于高效且有效的siRNA递送的无机NP方面仍存在若干挑战。使材料到达所选位点是重要的，然而最大的障碍可能是通过有效的内体逃逸或通过直接的胞质siRNA递送递送到胞质溶胶中。在器官和细胞水平的有效递送与具有低免疫原性应答的生物相容性载体结合将促进RNAi用于治疗遗传疾病的临床翻译。
Small interfering RNA (siRNA) is an effective method for regulating the expression of proteins, even “undruggable” ones that are nearly impossible to target through traditional small molecule therapeutics. Delivery to the cell and then to the cytosol is the primary requirement for realization of therapeutic potential of siRNA. We summarize recent advances in the design of inorganic nanoparticle with surface functionality and physicochemical properties engineered for siRNA delivery. Specifically, we discuss the main approaches developed so far to load siRNA into/onto NPs, and NP surface chemistry engineered for enhanced intracellular siRNA delivery, endosomal escape, and targeted delivery of siRNA to disease cells and tissues. Several challenges remain in developing inorganic NPs for efficient and effective siRNA delivery. Getting the material to the chosen site is important, however the greatest hurdle may well be delivery into the cytosol, either through efficient endosomal escape or by direct cytosolic siRNA delivery. Effective delivery at the organismic and cellular level coupled with biocompatible vehicles with low immunogenic response will facilitate the clinical translation of RNAi for the treatment of genetic diseases.