文献类型：期刊文献

英文题名：Biological Hyperthermia-Inducing Nanoparticles for Specific Remodeling of the Extracellular Matrix Microenvironment Enhance Pro-Apoptotic Therapy in Fibrosis

作者：Zhang, Jinru[1];Ji, Keqin[1];Ning, Yuanmeng[1];Sun, Lingna[1];Fan, Mingrui[1];Shu, Chunjie[1];Zhang, Ziqi[1];Tu, Tianyu[1];Cao, Jingyun[1];Gao, Feng[2];Chen, Yanzuo[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Minist Educ, Shanghai Key Lab New Drug Design,Pharmaceut Engn &, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Shanghai 200237, Peoples R China

年份：2023

卷号：17

期号：11

起止页码：10113

外文期刊名：ACS NANO

收录：;EI(收录号：20232514276538);WOS:【SCI-EXPANDED(收录号:WOS:001004733000001)】；

基金：This work was supported by the Natural Science Foundation of Shanghai (Grant No. 22ZR1415500).

语种：英文

外文关键词：fibrosis; exosome and liposome hybrid nanoparticles; hyperthermia; 2; 4-dinitrophenol; remodelingof the extracellular matrix microenvironment

摘要：The extracellular matrix (ECM) is a major driver of fibroticdiseasesand forms a dense fibrous barrier that impedes nanodrug delivery.Because hyperthermia causes destruction of ECM components, we developeda nanoparticle preparation to induce fibrosis-specific biologicalhyperthermia (designated as GPQ-EL-DNP) to improve pro-apoptotic therapyagainst fibrotic diseases based on remodeling of the ECM microenvironment.GPQ-EL-DNP is a matrix metalloproteinase (MMP)-9-responsive peptide,(GPQ)-modified hybrid nanoparticle containing fibroblast-derived exosomesand liposomes (GPQ-EL) and is loaded with a mitochondrial uncouplingagent, 2,4-dinitrophenol (DNP). GPQ-EL-DNP can specifically accumulateand release DNP in the fibrotic focus, inducing collagen denaturationthrough biological hyperthermia. The preparation was able to remodelthe ECM microenvironment, decrease stiffness, and suppress fibroblastactivation, which further enhanced GPQ-EL-DNP delivery to fibroblastsand sensitized fibroblasts to simvastatin-induced apoptosis. Therefore,simvastatin-loaded GPQ-EL-DNP achieved an improved therapeutic effecton multiple types of murine fibrosis. Importantly, GPQ-EL-DNP didnot induce systemic toxicity to the host. Therefore, the nanoparticleGPQ-EL-DNP for fibrosis-specific hyperthermia can be used as a potentialstrategy to enhance pro-apoptotic therapy in fibrotic diseases.