小干扰RNA
基因沉默
内吞作用
全身给药
癌症研究
RNA干扰
外渗
化学
细胞内
细胞生物学
体内
转染
医学
核糖核酸
细胞
免疫学
生物
基因
生物化学
生物技术
作者
Hyungjun Kim,Simseok A. Yuk,Alexandra M. Dieterly,Soonbum Kwon,Jinho Park,Fanfei Meng,Hytham H. Gadalla,Maria J Cadena,L. Tiffany Lyle,Yoon Yeo
出处
期刊:ACS Nano
[American Chemical Society]
日期:2021-03-01
卷期号:15 (3): 4576-4593
被引量:45
标识
DOI:10.1021/acsnano.0c08694
摘要
For systemic delivery of small interfering RNA (siRNA) to solid tumors, the carrier must circulate avoiding premature degradation, extravasate and penetrate tumors, enter target cells, traffic to the intracellular destination, and release siRNA for gene silencing. However, existing siRNA carriers, which typically exhibit positive charges, fall short of these requirements by a large margin; thus, systemic delivery of siRNA to tumors remains a significant challenge. To overcome the limitations of existing approaches, we have developed a carrier of siRNA, called "Nanosac", a noncationic soft polyphenol nanocapsule. A siRNA-loaded Nanosac is produced by sequential coating of mesoporous silica nanoparticles (MSNs) with siRNA and polydopamine, followed by removal of the sacrificial MSN core. The Nanosac recruits serum albumin, co-opts caveolae-mediated endocytosis to enter tumor cells, and efficiently silences target genes. The softness of Nanosac improves extravasation and penetration into tumors compared to its hard counterpart. As a carrier of siRNA targeting PD-L1, Nanosac induces a significant attenuation of CT26 tumor growth by immune checkpoint blockade. These results support the utility of Nanosac in the systemic delivery of siRNA for solid tumor therapy.
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