粘液
粘蛋白
纳米载体
生物物理学
化学
细胞穿透肽
细胞
细胞生物学
药物输送
生物化学
生物
有机化学
生态学
作者
Chenglong Ge,Jiandong Yang,Shanzhou Duan,Yong Liu,Fenghua Meng,Lichen Yin
出处
期刊:Nano Letters
[American Chemical Society]
日期:2020-02-10
卷期号:20 (3): 1738-1746
被引量:109
标识
DOI:10.1021/acs.nanolett.9b04957
摘要
The mucus layer and cell membrane are two major barriers against pulmonary siRNA delivery. Commonly used polycationic gene vectors can hardly penetrate the mucus layer due to the adsorption of mucin glycoproteins that trap and destabilize the polyplexes. Herein, guanidinated and fluorinated bifunctional helical polypeptides were developed to synchronizingly overcome these two barriers. The guanidine domain and α-helix facilitated trans-membrane siRNA delivery into macrophages, whereas fluorination of the polypeptides dramatically enhanced the mucus permeation capability by ∼240 folds, because incorporated fluorocarbon segments prevented adsorption of mucin glycoproteins onto polyplexes surfaces. Thus, when delivering TNF-α siRNA intratracheally, the top-performing polypeptide P7F7 provoked highly efficient gene knockdown by ∼96% at 200 μg/kg siRNA and exerted pronounced anti-inflammatory effect against acute lung injury. This study thus provides an effective strategy for transmucosal gene delivery, and it also renders promising utilities for the noninvasive, localized treatment of inflammatory pulmonary diseases.
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