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)-ultras...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.展开更多
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)+1 种基金Suzhou Science and Technology Development Project (No.SYS2019072), Collaborative Innovation Center of Suzhou NanoScience & Technology, the 111 project, Suzhou Key Laboratory ofNanotechnology and BiomedicineJoint InternationalResearch Laboratory of Carbon-Based Functional Materials andDevices。
文摘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.
