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

doi:10.7503/cjcu20190694

Abstract

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

CLC Number:

O647

TrendMD:

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

Figures/Tables 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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