植物多酚基元辅助递送siRNA的构效关系研究

doi:10.7503/cjcu20190694

高等学校化学学报 ›› 2020, Vol. 41 ›› Issue (4): 633.doi: 10.7503/cjcu20190694

• 庆祝《高等学校化学学报》复刊40周年专栏 • 上一篇下一篇

植物多酚基元辅助递送siRNA的构效关系研究

沈扬¹,朱方²,沈湾湾¹,范倩倩¹,李乙文^2,^*(),程义云^1,^3,^*()

^1. 华东师范大学生命科学学院, 上海市调控生物学重点实验室, 上海 200241
^2. 四川大学高分子科学与工程学院, 高分子材料工程国家重点实验室, 成都 610065
^3. 华南理工大学分子科学与工程学院, 华南软物质科学与技术高等研究院, 广州 510640

收稿日期:2019-12-19 出版日期:2020-04-10 发布日期:2020-01-17
通讯作者: 李乙文,程义云 E-mail:ywli@scu.edu.cn;yycheng@mail.ustc.edu.cn
基金资助:
国家自然科学基金(21725402, 21774079);上海市科委基金(17XD1401600)

Structure-function Relationship of Plant Polyphenols for Promoted siRNA Delivery ^†

SHEN Yang¹,ZHU Fang²,SHEN Wanwan¹,FAN Qianqian¹,LI Yiwen^2,^*(),CHENG Yiyun^1,^3,^*()

^1. Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China
^2. College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China
^3. School of Molecular Science and Engineering, South China Advanced Institute for Soft Matter Science and Technology, South China University of Technology, Guangzhou 510640, China

Received:2019-12-19 Online:2020-04-10 Published:2020-01-17
Contact: Yiwen LI,Yiyun CHENG E-mail:ywli@scu.edu.cn;yycheng@mail.ustc.edu.cn
Supported by:
† Supported by the National Natural Science Foundation of China(21725402, 21774079);the Shanghai Municipal Science and Technology Commission, China(17XD1401600)

摘要/Abstract

摘要：

表没食子儿茶素没食子酸酯(EGCG)在辅助低分子量阳离子聚合物递送siRNA的过程中表现优异, 但其本身是一个结构较为复杂的植物多酚基元, 可以进一步拆分为表没食子儿茶素(EGC)和没食子酸(GA)2种多酚基元. 而这2种基元分子同样具有抑制癌细胞、杀伤肿瘤细胞以及通过氢键和疏水相互作用力来结合蛋白质或核酸的能力. 本文拟探究各类植物多酚基元EGCG, EGC和GA结合核酸的能力和分别在辅助低分子量阳离子聚合物递送siRNA的过程中起到的作用. 实验结果表明, EGC辅助ε-聚赖氨酸(PLL)递送siRNA的效率仅次于EGCG, 而通过增加EGC的用量可以达到与EGCG接近的递送效果.

关键词: 植物多酚, 表没食子儿茶素没食子酸酯, 阳离子高分子, 基因递送, 基因治疗

Abstract:

Epigallocatechin gallate(EGCG) has demonstrated promising effects in promoting the delivery of siRNA by low molecular weight cationic polymers. EGCG can be further hydrolyzed into (-)-epigallocatechin(EGC) and gallic acid(GA) motifs. EGC and GA also have the effect of inhibiting cancer cells, killing tumor cells, and binding proteins or nucleic acids through the combination of hydrogen bonding and hydrophobic interactions. Herein, this study strives to perform a structure-function relationship investigation of plant polyphenol motifs(EGCG, EGC, and GA) in facilitation of condensation and delivery of siRNA by low molecular weight cationic polymers. It was found that EGCG exhibited the highest efficiency in promoting PLL-mediated siRNA delivery while EGC also showed a promising result, and the latter efficiency can be further improved by tailoring the dose of EGC in the complex.

Key words: Plant polyphenol, Epigallocatechin gallate, Cationic polymer, Gene delivery, Gene therapy

中图分类号:

O647

TrendMD:

沈扬, 朱方, 沈湾湾, 范倩倩, 李乙文, 程义云. 植物多酚基元辅助递送siRNA的构效关系研究. 高等学校化学学报, 2020, 41(4): 633.

SHEN Yang, ZHU Fang, SHEN Wanwan, FAN Qianqian, LI Yiwen, CHENG Yiyun. Structure-function Relationship of Plant Polyphenols for Promoted siRNA Delivery ^†. Chem. J. Chinese Universities, 2020, 41(4): 633.

图/表 4

Scheme 1 Schematic description of the structure-function relationship of plant polyphenols in promoting siRNA delivery mediated by low molecular weight polymers

Fig.1 Fluorescence spectra of siRNA-FAM(a), siRNA-FAM/EGCG(b), siRNA-FAM/EGC(c) and siRNA-FAM/GA(d) complex solutionsMolar ratio of EGC and GA to siRNA-FAM is equal to the ratio of EGCG/siRNA-FAM.

Fig.2 Size and morphology of the as-prepared complexDLS and TEM images of siRNA/EGCG/PLL(A), siRNA/EGC/PLL(B) and siRNA/GA/PLL(C) complexes. (D) Size and particle distribution index(PDI) of the siRNA/EGC/PLL complex prepared at different EGC to EGCG molar ratios. (E) DLS of the siRNA/EGCG/PLL(a) and siRNA/EGC/PLL(b) complexes. The molar ratio of used EGC to EGCG is 3∶1.

Fig.3 RNAi efficiency of the complexes on Hela-Luc cells(A) Delivery efficiency of siLuc assisted by EGCG(a), EGC(b), GA(c), EGC+GA(d) and EGCG+EGC+GA(e) in the presence of PLL; (B) RNAi efficiency of siRNA/EGC/PLL with different molar ratios of EGC/EGCG. EGCG was shown for comparison. ** P < 0.01, *** P < 0.001.

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植物多酚基元辅助递送siRNA的构效关系研究

Structure-function Relationship of Plant Polyphenols for Promoted siRNA Delivery ^†

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植物多酚基元辅助递送siRNA的构效关系研究

Structure-function Relationship of Plant Polyphenols for Promoted siRNA Delivery †

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Structure-function Relationship of Plant Polyphenols for Promoted siRNA Delivery ^†