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殷黎晨教授课题组在Nano Letters上发表论文

发布时间:2021-07-03访问量:24设置

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题目:

Fluorinated α-Helical Polypeptides Synchronize Mucus Permeation and Cell Penetration toward Highly Efficient Pulmonary siRNA Delivery against Acute Lung Injury

作者:

Chenglong Ge,1 Jiandong Yang,1 Shanzhou Duan,2 Yong Liu,1 Fenghua Meng,3 and Lichen Yin*,1

单位:

1Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, China.

2Department of Thoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China.

3Biomedical Polymers Laboratory and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and MaterialsScience, Soochow University, Suzhou 215123, China.

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.

影响因子:

12.279

分区情况:

一区

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