Fluorinated PEG-Polypeptide Polyplex Micelles Have Good Serum-Resistance and Low Cytotoxicity for Gene Delivery

Macromolecular Bioscience
Ting WuYe-Zi You

Abstract

A novel PEGylation polypeptide, poly(ethylene glycol)-b-poly(l-lysine)-b-poly(l-cysteine) (PEG-PLL-PCys) triblock copolymer is synthesized via the sequential ring-opening polymerization of amino acid N-carboxyanhydrides initiated by methoxypolyethylene glycol amine (mPEG-NH2 , Mw is 2 kDa). Subsequently, the obtained polypeptide is partially conjugated with fluorocarbon chains via disulfide exchange reaction. PLL segment can condense plasmid DNA through an electrostatic force to form a complex core, PEG segment surrounding the complex like a corona can prevent the complex from precipitation and reduce the adsorption of serum, while PCys segment with fluorocarbon can enhance the cellular uptake and the stability of the formed polyplex micelles in physiological conditions. Experiment results exhibit that the fluorinated polypeptides have low cytotoxicity and good gene transfection efficiency even in the presence of 50% fetal bovine serum.

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Citations

Aug 18, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Chen ZhangHui Chao
Jun 9, 2020·Drug Delivery and Translational Research·Lian XueDaniel J Siegwart
Mar 10, 2021·Chemical Society Reviews·Jia Lv, Yiyun Cheng
Dec 29, 2020·Chemical Reviews·Stephanie FuchsMinglin Ma
May 4, 2021·Chemical Reviews·Ramya KumarTheresa M Reineke
Dec 6, 2017·The Journal of Organic Chemistry·Alexander Q CusumanoJoshua G Pierce
Sep 4, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Jun LiXiao-Qi Yu

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