文献类型： 外文期刊

作者： Ma, Zhongzheng ¹ ; Zheng, Yang ⁴ ; Chao, Zijian ¹ ; Chen, Hongtao ⁵ ; Zhang, Yunhui ¹ ; Yin, Meizhen ⁵ ; Shen, Jie ¹ ; Yan, Shuo ¹ ;

作者机构： 1.China Agr Univ, Dept Plant Biosecur, Coll Plant Protect, Beijing 100193, Peoples R China

2.China Agr Univ, MOA Key Lab Pest Monitoring & Green Management, Coll Plant Protect, Beijing 100193, Peoples R China

3.Beijing Acad Agr & Forestry Sci, Inst Plant Protect, Beijing 100097, Peoples R China

4.Yangzhou Univ, Coll Hort & Plant Protect, Yangzhou 225002, Jiangsu, Peoples R China

5.Beijing Univ Chem Technol, State Key Lab Chem Resource Engn, Beijing Lab Biomed Mat, Beijing 100029, Peoples R China

关键词： Cellular uptake; Clathrin; Endocytosis; dsRNA; Nanocarrier; RNA interference

期刊名称：JOURNAL OF NANOBIOTECHNOLOGY （ 影响因子：9.429； 五年影响因子：11.509 ）

ISSN：

年卷期： 2022 年 20 卷 1 期

页码：

收录情况： SCI

摘要： Nanoparticles have been widely applied as gene carrier for improving RNA interference (RNAi) efficiency in medical and agricultural fields. However, the mechanism and delivery process of nanoparticle-mediated RNAi is not directly visualized and elucidated. Here we synthesized a star polymer (SPc) consisted of a hydrophilic shell with positively-charged tertiary amine in the side chain, which was taken as an example to investigate the mechanism in gene delivery. The SPc could assemble with dsRNA spontaneously through electrostatic force, hydrogen bond and van der Waals force. Interestingly, the SPc could protect dsRNA from degradation by RNase A and insect hemolymph, thus remarkably increasing the stability of dsRNA. Meanwhile, the SPc could efficiently promote the cellular uptake and endosomal escape for intracellular spreading of dsRNA. Transcriptome analysis revealed that the SPc could up-regulate some key genes such as Chc, AP2S1 and Arf1 for activating clathrin-mediated endocytosis. Furthermore, the suppression of endocytosis hindered the cellular uptake of SPc-delivered dsRNA in vitro, and the subsequent RNAi effect was also disappeared in vivo. To our knowledge, our study is the first direct visualization of the detailed cellular delivery process and mechanism of nanocarrier-mediated gene delivery. Above mechanism supports the application of nanocarrier-based RNAi in gene therapy and pest management.