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ROS responsive polyethylenimine-based fluorinated polymers for enhanced transfection efficiency and lower cytotoxicity
Hua, Peng; Yang, Donglin; Chen, Ruie; Qiu, Peiqi; Chen, Meiwan
2022-07-29
Source PublicationBosnian Journal of Basic Medical Sciences
ISSN1512-8601
Volume22Issue:4Pages:593-607
Abstract

Cationic polymer polyethylenimine (PEI) plays a crucial role in gene delivery. However, high molecular weight PEI leads to higher efficient transfection efficacy and higher cytotoxicity, while low molecular weight PEI exhibits lower transfection performance with lower toxicity. Therefore, effective chemical modification of PEI is required to enhance transfection activity and improve biocompatibility. Here, reactive oxygen species (ROS) responsive PEI-based fluorinated polymers (TKPF) with three degrees of fluorination (TKPF 12.5%, TKPF 25%, and TKPF 50%) were designed and synthesized by crosslinking low molecular weight PEI (PEI 1.8K) with a thioketal (TK) linker and then modifying heptafluorobutyric anhydride onto their surface. Fluorination reduced the positive charge density and endowed hydrophobic and lipopho-bic characteristics to resist serum interactions. The fluorophilic effect mediated efficient cellular uptake and endosomal escape while ROS-responsive TK linker allowed the polyplex disassembly to decrease the cytotoxicity of the polycations and improve the release of payloads at specific sites. TKPFs attained superior transfection efficiency in multiple cell lines (293TN cells and B16F10 cells) in vitro and showed excellent biocompatibility. TKPFs also exhibited great serum resistance in gene delivery and TKPF 50% transfected nearly 80% cells in the presence of 70% FBS. These results demonstrate that the fluorination and ROS responsiveness combined polycations are excellent gene-delivery vectors with serum-resistant capacity for further application.

KeywordFluorination Polycation Ros-responsive Serum-resistant Transfection
DOI10.17305/bjbms.2021.6704
URLView the original
Language英語English
Scopus ID2-s2.0-85134906953
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Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
AffiliationState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau,
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Hua, Peng,Yang, Donglin,Chen, Ruie,et al. ROS responsive polyethylenimine-based fluorinated polymers for enhanced transfection efficiency and lower cytotoxicity[J]. Bosnian Journal of Basic Medical Sciences,2022,22(4):593-607.
APA Hua, Peng,Yang, Donglin,Chen, Ruie,Qiu, Peiqi,&Chen, Meiwan.(2022).ROS responsive polyethylenimine-based fluorinated polymers for enhanced transfection efficiency and lower cytotoxicity.Bosnian Journal of Basic Medical Sciences,22(4),593-607.
MLA Hua, Peng,et al."ROS responsive polyethylenimine-based fluorinated polymers for enhanced transfection efficiency and lower cytotoxicity".Bosnian Journal of Basic Medical Sciences 22.4(2022):593-607.
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