“Zip-to-Cytosol”: Glutathione-Cleavable Fluorinated Polyplexes Deliver siRNA at Single-Digit Nanomolar Dose with >90% Gene Silencing

Bioconjugate Chemistry 2026

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Authors: Yue Wang, Jingyi Wang, Hu Cui, Liuwei Zhang, Ruohan Zhao, Zhongwang Liu, Q Zhong, Xin Wang, Yaojie Wang, Qixian Chen, Haining Yu, Yan Zhao
DOI: 10.1021/acs.bioconjchem.5c00554
Cited by: 2
References: 28

Abstract

A fluorinated, disulfide-cross-linked polyplex platform (PFND) was developed for safe and potent cytosolic delivery of siRNA. Branched PEI (25 kDa) was first perfluoro-acylated to yield a membrane-zipper PF backbone, followed by orthogonal installation of azide (PF-N 3 ) and strained alkyne (PF-DBCO) handles that undergo in situ copper-free click cross-linking in the presence of siRNA. The resulting 60 nm polyplexes (PDI < 0.1, ζ potential of approximately +22 mV) are stable in 10 mg mL –1 heparin (

Fields of Study & Subjects

RNA Interference and Gene Delivery Virus-based gene therapy research CRISPR and Genetic Engineering

Publication details

Journal / source
Bioconjugate Chemistry
Publisher
American Chemical Society (ACS)
Volume
37
Issue
1
Pages
160–168
Publication date
10 January 2026
Language
EN