Non-viral gene coating modified IOL delivering PDGFR-αshRNA interferes with the fibrogenic process to prevent posterior capsular opacification  

作　　者：Jiahao Wang Yulin Hu Yuemei Han Qiuna Fang Zhirong Chen Yajia Wang Peiyi Zhao Hui Wang Quankui Lin 

机构地区：[1]Department of Biomaterials,National Engineering Research Center of Ophthalmology and Optometry,School of Biomedical Engineering,School of Ophthalmology and Optometry,Eye Hospital,Wenzhou Medical University,Wenzhou 325027,China

出　　处：《Regenerative Biomaterials》2023年第1期655-669,共15页再生生物材料（英文版）

基　　金：supported by the Zhejiang Provincial Natural Science Foundation(LR23H180001);the Key Scientific and Technological Innovation Projects in Wenzhou(ZY2021002);Medical&Health Technology Program of Zhejiang Province(2022RC051);the Zhejiang Science and Technology Program of Traditional Chinese Medicine(2022ZB220).

摘　　要：Posterior capsule opacification(PCO),the most common complication after cataract surgery,is caused by the proliferation,migration and epithelial-mesenchymal transition(EMT)of residual lens epithelial cells in the capsule bag.Although the surface modification and drug loading of intraocular lens(IOLs)have been effective in preventing PCO to some extent,the intraocular safety of anti-proliferative drug application is still a major limitation in clinical application.In this study,we used non-viral gene delivery systems in combination with layer-by-layer(LBL)self-assembly technology,and the modified IOL could effectively prevent the development of PCO by interfering with the EMT process mediated by the platelet-derived growth factor receptor-α(PDGFR-α).Herein,the gene fragments were wrapped by electrostatic conjugation using polyethyleneimine-graft-poly(ethylene glycol)to form gene complexes.Gene complexes were characterized by dynamic light scattering,transmission electron microscopy(TEM)and agarose gel electrophoresis,and evaluated for storage and serum stability.The layer assembly behavior of the IOL surface,changes in optical properties and the release behavior of the gene complexes were characterized using quartz crystal microbalance,UV-vis,contact angle and TEM.In vitro experiments showed that the IOL coating has good bio-compatibility and can achieve the corresponding transfection effect,and the released gene complexes exhibited excellent cell internalization and lysosomal escape behaviors,as well as effective inhibition of PDGFR-αexpression and its mediated EMT process.The early PCO prevention effect and bio-compatibility evaluation of the modified IOL in vivo were evaluated by implantation into animal eyes.This study provides a new strategy for the development of surface modifications of small nucleic acid drugs and non-toxic EMT interference therapies for PCO.

关 键 词：intraocular lens posterior capsule opacification surface modification non-viral gene delivery system epithelial-mesenchymal transformation 

分 类 号：R318[医药卫生—生物医学工程]