Cardiomyocyte-targeted anti-inflammatory nanotherapeutics against myocardial ischemia reperfusion (IR) injury  

作　　者：Min Lan Mengying Hou Jing Yan Qiurong Deng Ziyin Zhao Shixian Lv Juanjuan Dang Mengyuan Yin Yong Ji Lichen Yin 

机构地区：[1]Institute of Functional Nano and Soft Materials(FUNSOM),Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices,Soochow University,Suzhou 215123,China [2]Department of Cardiothoracic Surgery,Wuxi People’s Hospital Affiliated to Nanjing Medical University,Wuxi 214023,China

出　　处：《Nano Research》2022年第10期9125-9134,共10页纳米研究（英文版）

基　　金：funding support from the National Natural Science Foundation of China(No.52033006 and 51873142);Suzhou Science and Technology Development Project(No.SYS2019072) Science Foundation of China (No. 52033006 and 51873142);Suzhou Science and Technology Development Project (No.SYS2019072), Collaborative Innovation Center of Suzhou NanoScience & Technology, the 111 project, Suzhou Key Laboratory ofNanotechnology and Biomedicine;Joint InternationalResearch Laboratory of Carbon-Based Functional Materials andDevices。

摘　　要：Myocardial ischemia reperfusion(IR)injury is closely related to the overwhelming inflammation in the myocardium.Herein,cardiomyocyte-targeted nanotherapeutics were developed for the reactive oxygen species(ROS)-ultrasensitive co-delivery of dexamethasone(Dex)and RAGE small interfering RNA(siRAGE)to attenuate myocardial inflammation.PPTP,a ROSdegradable polycation based on PGE2-modified,PEGylated,ditellurium-crosslinked polyethylenimine(PEI)was developed to surface-decorate the Dex-encapsulated mesoporous silica nanoparticles(MSNs),which simultaneously condensed siRAGE and gated the MSNs to prevent the Dex pre-leakage.Upon intravenous injection to IR-injured rats,the nanotherapeutics could be efficiently transported into the inflamed cardiomyocytes via PGE2-assisted recognition of over-expressed E-series of prostaglandin(EP)receptors on the cell membranes.Intracellularly,the over-produced ROS degraded PPTP into small segments,promoting the release of siRAGE and Dex to mediate effective RAGE silencing(72%)and cooperative antiinflammatory effect.As a consequence,the nanotherapeutics notably suppressed the myocardial fibrosis and apoptosis,ultimately recovering the systolic function.Therefore,the current nanotherapeutics represent an effective example for the codelivery and on-demand release of nucleic acid and chemodrug payloads,and might find promising utilities toward the synergistic management of myocardial inflammation.

关 键 词：small interfering RNA(siRNA)delivery reactive oxygen species(ROS)responsiveness ditellurium-crosslinked polyethylenimine(PEI) myocardial ischemia reperfusion injury ANTI-INFLAMMATION 

分 类 号：R542.2[医药卫生—心血管疾病]