Regulating intracellular fate of siRNA by endoplasmic reticulum membrane-decorated hybrid nanoplexes

Chong Qiu, Hu-Hu Han, Jing Sun, Hai-Tao Zhang, Wei Wei, Shi-He Cui, Xin Chen, Jian-Cheng Wang () and Qiang Zhang
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Chong Qiu: Peking University
Hu-Hu Han: Peking University
Jing Sun: Peking University
Hai-Tao Zhang: Central South University
Wei Wei: Peking University
Shi-He Cui: Peking University
Xin Chen: Peking University
Jian-Cheng Wang: Peking University
Qiang Zhang: Peking University

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Most cationic vectors are difficult to avoid the fate of small interfering RNA (siRNA) degradation following the endosome-lysosome pathway during siRNA transfection. In this study, the endoplasmic reticulum (ER) membrane isolated from cancer cells was used to fabricate an integrative hybrid nanoplexes (EhCv/siRNA NPs) for improving siRNA transfection. Compared to the undecorated Cv/siEGFR NPs, the ER membrane-decorated EhCv/siRNA NPs exhibits a significantly higher gene silencing effect of siRNA in vitro and a better antitumor activity in nude mice bearing MCF-7 human breast tumor in vivo. Further mechanistic studies demonstrate that functional proteins on the ER membrane plays important roles on improving cellular uptake and altering intracellular trafficking pathway of siRNA. It is worth to believe that the ER membrane decoration on nanoplexes can effectively transport siRNA through the endosome-Golgi-ER pathway to evade lysosomal degradation and enhance the silencing effects of siRNA.

Date: 2019
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DOI: 10.1038/s41467-019-10562-w

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