Drug Delivery and Translational Research: PEI fluorination reduces toxicity and promotes liver-targeted siRNA delivery
作者：Lian Xue, Yunfeng Yan,* Petra Kos, Xiaoping Chen, and Daniel J. Siegwart*
關鍵字：Polyethyleneimine (PEI), siRNA, Nanoparticles, Gene silencing
論文來源：期刊
具體來源：Drug Delivery and Translational Research
發表時間：2020年
Polyethyleneimine (PEI) has been extensively investigated as an efficient carrier for nucleic acid delivery. Yet, it suffers from a
high toxicity profile that hinders clinical translation. Fluorination has proven to be a valid approach to reduce the cytotoxicity of
PEI and improve the in vitro siRNA delivery potency. Hydrophobicity and lipophobicity can be controllably introduced into the
side chains of PEI. However, the effect of fluorination on siRNA delivery in vivo, particularly the biodistribution of siRNA
polyplex nanoparticles with fluorinated PEIs, has not been extensively explored. Here, we introduce two series of fluorinated
PEIs via amidation with ethyl trifluoroacetate and perfluorobutyryl chloride. Fluorination substantially improved the performance of PEI for siRNA delivery by reducing the cytotoxicity to MDA-MB-231 cells. Importantly, fluorinated PEI enabled the
major accumulation of siRNA polyplex nanoparticles in the liver while non-fluorinated PEI delivered siRNA nanoparticles
mainly to the lungs after intravenous administration to mice. It is envisioned that fluorination may be an important general
strategy for lowering toxicity of cationic polymers, and that the fluorination-induced alteration of biodistribution may be
applicable for improved delivery to different organs.