ROS-responsive&scavenging NO nanomedicine for vascular diseases treatment by inhibiting endoplasmic reticulum stress and improving NO bioavailability  

作　　者：Jian Li Jvhong Zhang Pengcheng Yu Han Xu Meihui Wang Zhebin Chen Bo Yu Jing Gao Qiao Jin Fan Jia Jian Ji Guosheng Fu 

机构地区：[1]Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province,Department of Cardiology,Sir Run Run Shaw Hospital,Zhejiang University,Hangzhou,310016,PR China [2]MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education,Department of Polymer Science and Engineering,Zhejiang University,Hangzhou,PR China

出　　处：《Bioactive Materials》2024年第7期239-252,共14页生物活性材料（英文）

基　　金：supported by the National Key Research and Development Program of China (2022YFB3807300);the National Natural Science Foundation of China (51933009,82370427,22305219);the Fundamental Research Funds for the Central Universities,China (26-2023-00074);the Natural Science Foundation of Zhejiang Province,China (No.LY20H020005);The Zhejiang Provincial Traditional Chinese Medicine Science and Technology Plan,China (2022ZX012);The Province and Central Administration-Zhejiang Provincial Health Commission,China (WKJ-ZJ-2209).

摘　　要：Vascular diseases seriously threaten human life and health.Exogenous delivery of nitric oxide(NO)represents an effective approach for maintaining vascular homeostasis during pathological events.However,the overproduction of reactive oxygen species(ROS)at vascular injury sites would react with NO to produce damaging peroxynitrite(ONOO)species and limit the therapeutic effect of NO.Hence,we design a ROS-responsive NO nanomedicine(t-PBA&NO NP)with ROS scavenging ability to solve the dilemma of NO-based therapy.t-PBA&NO NP targets NO and anti-oxidant ethyl caffeate(ECA)to the injury sites via collagen IV homing peptide.The ROS-triggered ROS depletion and ECA release potently alleviate local oxidative stress via ROS scavenging,endoplasmic reticulum and mitochondrial regulation.It subsequently maximizes vascular modulation effects of NO,without production of harmful compounds,reactive nitrogen species(RNS).Therefore,it significantly increases competitiveness of human umbilical vein endothelial cells(HUVECs)over human aortic smooth muscle cells(HASMCs)both in vitro and in vivo.The strategy proved effective in inducing faster re-endothelialization,inhibiting neointimal formation and restoring vascular homeostasis.The synergy between ROS depletion and NO therapy served as a new inspiration for the treatment of cardiovascular diseases and other ROS-associated illnesses.

关 键 词：Cardiovascular diseases Nitric oxide Reactive oxygen species Endoplasmic reticulum stress NANOMEDICINE 

分 类 号：R54[医药卫生—心血管疾病]