Early initiation of ARBs without blood pressure risk via neutrophil membrane-fused pH-sensitive liposomes to reduce cardiomyocyte apoptosis after acute myocardial infarction  

作　　者：Jinfeng Gao Wusiman Yakufu Hongbo Yang Yanan Song Qiaozi Wang Qiyu Li Haipeng Tan Jing Chen Dili Sun Zhengmin Wang Jinyan Zhang Xueyi Weng Juying Qian Zhiqing Pang Qibing Wang Zheyong Huang Junbo Ge 

机构地区：[1]Department of Cardiology,Zhongshan Hospital,Fudan University.Shanghai Institute of Cardiovascular Diseases,Shanghai 200032,China [2]National Clinical Research Center for Interventional Medicine&Shanghai Clinical Research Center for Interventional Medicine,180 Feng Lin Road,Shanghai 200032,China [3]Institute of Biomedical Sciences,Fudan University,Shanghai 200032,China [4]School of Pharmacy,Fudan University,Key Laboratory of Smart Drug Delivery,Ministry of Education,826 Zhangheng Road,Shanghai 200032,China

出　　处：《Nano Research》2023年第7期9894-9905,共12页纳米研究（英文版）

基　　金：The authors thank the Shiyanjia Lab(www.shiyanjia.com)for TEM measurements.The authors are grateful to Ms.Xiao Guo at the Joint Live Small Animal Imaging Laboratory of Fudan University Shanghai Medical College-PerkinElmer Company,for her technical support with the use of the in vivo imaging system.This work was financially supported by the National Key Research and Development Program of China(No.2016YFC1301200);the National Natural Science Foundation of China(Nos.82070281,81870269,and 82170524);Shanghai Clinical Research Center for Interventional Medicine(No.19MC1910300).

摘　　要：Activation of the local renin-angiotensin system(RAS)promotes cardiomyocyte apoptosis and cardiac remodeling after acute myocardial infarction(AMI).As an anti-RAS drug,the effect of Valsartan in the early stage of acute MI is limited by its low drug concentration in the heart and low dosage.Here,by exploiting the inherent nature of neutrophils migrating to the injured myocardium and the local low-pH microenvironment caused by ischemia and hypoxia after myocardial infarction,we designed nanocarrier(NSLP)-hybridized neutrophil membranes and pH-sensitive liposomes(SLPs)for the delivery of Valsartan(NSLPVal).These functional nanocarriers could mimic neutrophils and are homed to the injured heart;they were also found to respond to a low-pH microenvironment.In the mouse model of MI,we found that NSLP-Val could target the infarct marginal zone and release Valsartan locally in the low-pH microenvironment without affecting hemodynamic stability.Further,locally released angiotensin receptor inhibitors reduced the infarct size and inflammatory response by inhibiting cardiomyocytes.Ultimately,NSLP-Val improved cardiac function and inhibited cardiac hypertrophy and fibrosis.

关 键 词：VALSARTAN early initiation cardiomyocyte apoptosis blood pressure myocardial infarction 

分 类 号：R542.22[医药卫生—心血管疾病]