C176-loaded and phosphatidylserine-modified nanoparticles treat retinal neovascularization by promoting M2 macrophage polarization  

作　　者：An Shao Lulu Jin Yanni Ge Ziqiang Ye Mingyu Xu Yifan Zhou Yingyu Li Linyan Wang Pinglong Xu Kai Jin Zhengwei Mao Juan Ye 

机构地区：[1]Eye Center,The Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou,310009,China [2]MOE Key Laboratory of Macromolecular Synthesis and Functionalization,Department of Polymer Science and Engineering,Zhejiang University,Hangzhou,310027,China [3]MOE Key Laboratory of Biosystems Homeostasis&Protection and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology,Life Sciences Institute,Zhejiang University,Hangzhou,310030,China

出　　处：《Bioactive Materials》2024年第9期392-405,共14页生物活性材料（英文）

基　　金：supported by Key Program of the National Natural Science Foundation of China(82330032);Natural Science Foundation of China(82201195);National Natural Science Foundation Regional Innovation and Development Joint Fund(U20A20386);Key Research and Development Program of Zhejiang Province(2024C03204).

摘　　要：Retinal neovascularization(RNV),a typical pathological manifestation involved in most neovascular diseases,causes retinal detachment,vision loss,and ultimately irreversible blindness.Repeated intravitreal injections of anti-VEGF drugs were developed against RNV,with limitations of incomplete responses and adverse effects.Therefore,a new treatment with a better curative effect and more prolonged dosage is demanding.Here,we induced macrophage polarization to anti-inflammatory M2 phenotype by inhibiting cGAS-STING signaling with an antagonist C176,appreciating the role of cGAS-STING signaling in the retina in pro-inflammatory M1 polarization.C176-loaded and phosphatidylserine-modified dendritic mesoporous silica nanoparticles were constructed and examined by a single intravitreal injection.The biosafe nanoparticles were phagocytosed by retinal macrophages through a phosphatidylserine-mediated“eat me”signal,which persistently release C176 to suppress STING signaling and thereby promote macrophage M2 polarization specifically.A single dosage can effectively alleviate pathological angiogenesis phenotypes in murine oxygen-induced retinopathy models.In conclusion,these C176-loaded nanoparticles with enhanced cell uptake and long-lasting STING inhibition effects might serve as a promising way for treating RNV.

关 键 词：Retinal neovascularization Macrophage polarization cGAS-STING pathway NANOCARRIER 

分 类 号：R774.1[医药卫生—眼科]