Synthesis and anti-HCC activity of full 2ʹ-F/OMe-siRNA encapsulated with neutral cytidinyl/cationic lipid
10.16438/j.0513-4870.2022-1345
- VernacularTitle:全2ʹ-F/OMe-siRNA的设计合成及其新型混合脂材纳米制剂抗肝癌活性评价
- Author:
Yu-jing GAO
1
;
Xi-xian WANG
2
;
Yu-fei PAN
2
;
Quan-xin WANG
2
;
Yue-jie ZHU
2
;
De-lin PAN
1
;
Zhu GUAN
2
;
Zhen-jun YANG
2
Author Information
1. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
- Publication Type:Research Article
- Keywords:
siRNA;
full 2ʹ-modification;
anti-HCC;
Ago2;
DNCA/CLD
- From:
Acta Pharmaceutica Sinica
2023;58(6):1634-1640
- CountryChina
- Language:Chinese
-
Abstract:
A variety of full 2ʹ-F/OMe-modified siRNAs were designed and synthesized, and the activity against hepatocellular carcinoma Huh-7 and HepG2 cells was evaluated. K&A DNA/RNA H-8 synthesizer was used to synthesize siRNAs, and neutral cytidinyl lipid DNCA mixed with cationic lipid CLD were used to transfect siRNA. By RT-qPCR and CCK-8 assay, the target gene silence and the proliferation of Huh-7 and HepG2 cells were detected. The siRNAs loading into Ago2 protein was detected by RNA-binding protein immunoprecipitation. Drug uptake and cell apoptosis were detected by flow cytometry, and the expression of PLK1 protein was detected by Western blot. Partial full 2ʹ-F/OMe modified siRNAs, especial siPLK1A3, increased the uptake of Huh-7 cells, enhanced their binding to Ago2 and gene silencing activity, down-regulated PLK1 protein, as well as induced more Huh-7 cell apoptosis and proliferation inhibition activity. It provides important data for the development of novel siRNA modification patterns and anti-HCC formulations.
