An ischemic area-targeting,peroxynitrite-responsive,biomimetic carbon monoxide nanogenerator for preventing myocardial ischemia-reperfusion injury  

作　　者：Jinyan Zhang Liwei Liu Zhen Dong Xicun Lu Wenxuan Hong Jin Liu Xiaoyi Zou Jinfeng Gao Hao Jiang Xiaolei Sun Kai Hu Youjun Yang Junbo Ge Xiao Luo Aijun Sun 

机构地区：[1]Department of Cardiology,Zhongshan Hospital,Fudan University,China [2]Shanghai Institute of Cardiovascular Diseases,Shanghai,China [3]Institutes of Biomedical Sciences,Fudan University,Shanghai,China [4]NHC Key Laboratory of Viral Heart Diseases,Shanghai,China [5]Key Laboratory of Viral Heart Diseases,Chinese Academy of Medical Sciences,China [6]State Key Laboratory of Bioreactor Engineering,Shanghai Key Laboratory of Chemical Biology,School of Pharmacy,East China University of Science and Technology,Shanghai,200237,China [7]Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development,School of Chemistry and Molecular Engineering,East China Normal University,Shanghai,China

出　　处：《Bioactive Materials》2023年第10期480-494,共15页生物活性材料（英文）

基　　金：support by the National Natural Science Foundation of China(81900353,82270264,T2288101,82130010,21908065,22078098,22278138);the National Science Fund for Distinguished Young Scholars(817200010);the Basic research projects of Shanghai Science and Technology Commission(22JC1400500);the Innovation Program of Shanghai Municipal Education Commission.

摘　　要：Myocardial ischemia-reperfusion (MI/R) injury is common in patients who undergo revascularization therapy for myocardial infarction, often leading to cardiac dysfunction. Carbon monoxide (CO) has emerged as a therapeutic molecule due to its beneficial properties such as anti-inflammatory, anti-apoptotic, and mitochondrial biogenesis-promoting properties. However, its clinical application is limited due to uncontrolled release, potential toxicity, and poor targeting efficiency. To address these limitations, a peroxynitrite (ONOO )-triggered CO donor (PCOD585) is utilized to generate a poly (lactic-co-glycolic acid) (PLGA)-based, biomimetic CO nanogenerator (M/PCOD@PLGA) that is coated with the macrophage membrane, which could target to the ischemic area and neutralize proinflammatory cytokines. In the ischemic area, local produced ONOO triggers the continuous release of CO from M/PCOD@PLGA, which efficiently ameliorates MI/R injury by clearing harmful ONOO , attenuating the inflammatory response, inhibiting cardiomyocyte apoptosis, and promoting mitochondrial biogenesis. This study provides a novel insight into the safe therapeutic use of CO for MI/R injury by utilizing a novel CO donor combined with biomimetic technology. The M/PCOD@PLGA nanogenerator offers targeted delivery of CO to the ischemic area, minimizing potential toxicity and enhancing therapeutic efficacy.

关 键 词：Ischemia-reperfusion injury Macrophage membrane MITOCHONDRIA Inflammation PEROXYNITRITE 

分 类 号：R318[医药卫生—生物医学工程]