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郭天瑛课题组 | JOURNAL OF CONTROLLED RELEASE

发布人:    发布时间:2024/03/15   浏览次数:

Tet1 peptide and zinc (II)-adenine multifunctional module functionalized polycations as efficient siRNA carriers for Parkinson's disease


By

Liu, WJ (Liu, Weijie) [1] ; Ma, CC (Ma, Chunchao) [2] ; Cao, JP (Cao, Junpeng) [1] ; Zhou, H (Zhou, Hao) [3] ; Guo, TY (Guo, Tianying) [1]

Source

JOURNAL OF CONTROLLED RELEASE

Volume

367

Page

316-326

DOI

10.1016/j.jconrel.2024.01.042

Published

MAR 2024

Early Access

JAN 2024

Indexed

2024-03-11

Document Type

Article

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Abstract

A bioreducible Zn (II)-adenine multifunctional module (BS) and Tet1 peptide were used to modify lowmolecular-weight PEI3.5k (polyethyleneimine with molecular weight of 3.5 kDa)into a siRNA vector Zn-PB-T with high transfection efficiency in neurons. A GSH-responsive breakable disulfide spacer was introduced into BS to realize the controlled release of siRNA from the polyplexes in cytoplasm. Zn-PB showed >90% transfection rates in multiple cell lines (3 T3, HK-2, HepG2, 293 T, HeLa, PANC-1),and 1.8-folds higher EGFP knockdown rates than commercial Lipo2k in normal cell line 293 T and cancer cell line HepG2. And Zn-PB-T1 showed 4.7-4.9- and 8.0-8.1-folds higher transfection efficiency comparing to commercial Lipo(2k )and PEI25k (polyethyleneimine with molecular weight of 25 kDa) in PC12 cells respectively, 2.1-fold EGFP gene silencing efficiency (96.6% EGFP knockdown rates) superior to commercial Lipo2k in neurons. In Parkinson's model, Zn-PBT1/SNCA-siRNA can effectively protect neurons against MPP+-induced cell death and apoptosis, increasing the cell survival rate to 84.6% and reducing the cell apoptosis rate to 10.8%. This work demonstrated the promising application prospects of the resulting efficient siRNA carriers in siRNA-mediated gene therapy of Parkinson's disease.