{"title":"用复合靶向多酚纳米粒子治疗心肌缺血再灌注损伤的昼夜节律依赖疗法","authors":"Bosong Zhang, Cao Wang, Mingyue Guo, Fuxing Zhu, Zhenqiang Yu, Wenxiang Zhang, Wenyu Li, Yijian Zhang, Weiming Tian","doi":"10.1021/acsnano.4c07690","DOIUrl":null,"url":null,"abstract":"<p><p>Myocardial ischemia-reperfusion (IR) injury is a severe rhythmic disease with a high prevalence in the early morning. IR injury has a significant circadian rhythm in reactive oxygen species (ROS) and inflammation levels. The development of rhythmic drugs has become a priority in myocardial IR injury. In this study, resveratrol (RES) and proanthocyanidins (OPC) were utilized to design nanoparticles (NPs), with hyaluronic acid (HA) as the core, grafted with MMP-targeting peptides to improve delivery to injured myocardial regions (HA-RES-OPC-MMP NPs). NPs significantly scavenged ROS, attenuated inflammation, and activated the rhythm gene. Notably, the difference in therapeutic effects on myocardial IR injury in mice at Zeitgeber time (ZT)1 and ZT13 confirms that NPs are rhythm-dependent drugs. At ZT13, echocardiographic and MRI confirm that IR injury in mice was not as severe as at ZT1, yet NPs were also less effective in treatment. Further, <i>Per1/2</i> knockout mice confirmed the rhythm-dependent treatment of myocardial IR injury by NPs. Molecular studies have shown that rhythmic characteristics of inflammation and <i>Sirt1</i> transcript levels are the main reasons for the different rhythmic therapeutic effects of NPs. Circadian rhythm-dependent treatment of HA-RES-OPC-MMP NPs has excellent potential for more precise treatment of myocardial IR injury in the future.</p>","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":null,"pages":null},"PeriodicalIF":15.8000,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Circadian Rhythm-Dependent Therapy by Composite Targeted Polyphenol Nanoparticles for Myocardial Ischemia-Reperfusion Injury.\",\"authors\":\"Bosong Zhang, Cao Wang, Mingyue Guo, Fuxing Zhu, Zhenqiang Yu, Wenxiang Zhang, Wenyu Li, Yijian Zhang, Weiming Tian\",\"doi\":\"10.1021/acsnano.4c07690\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Myocardial ischemia-reperfusion (IR) injury is a severe rhythmic disease with a high prevalence in the early morning. IR injury has a significant circadian rhythm in reactive oxygen species (ROS) and inflammation levels. The development of rhythmic drugs has become a priority in myocardial IR injury. In this study, resveratrol (RES) and proanthocyanidins (OPC) were utilized to design nanoparticles (NPs), with hyaluronic acid (HA) as the core, grafted with MMP-targeting peptides to improve delivery to injured myocardial regions (HA-RES-OPC-MMP NPs). NPs significantly scavenged ROS, attenuated inflammation, and activated the rhythm gene. Notably, the difference in therapeutic effects on myocardial IR injury in mice at Zeitgeber time (ZT)1 and ZT13 confirms that NPs are rhythm-dependent drugs. At ZT13, echocardiographic and MRI confirm that IR injury in mice was not as severe as at ZT1, yet NPs were also less effective in treatment. Further, <i>Per1/2</i> knockout mice confirmed the rhythm-dependent treatment of myocardial IR injury by NPs. Molecular studies have shown that rhythmic characteristics of inflammation and <i>Sirt1</i> transcript levels are the main reasons for the different rhythmic therapeutic effects of NPs. Circadian rhythm-dependent treatment of HA-RES-OPC-MMP NPs has excellent potential for more precise treatment of myocardial IR injury in the future.</p>\",\"PeriodicalId\":21,\"journal\":{\"name\":\"ACS Nano\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":15.8000,\"publicationDate\":\"2024-10-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Nano\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://doi.org/10.1021/acsnano.4c07690\",\"RegionNum\":1,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Nano","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1021/acsnano.4c07690","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Circadian Rhythm-Dependent Therapy by Composite Targeted Polyphenol Nanoparticles for Myocardial Ischemia-Reperfusion Injury.
Myocardial ischemia-reperfusion (IR) injury is a severe rhythmic disease with a high prevalence in the early morning. IR injury has a significant circadian rhythm in reactive oxygen species (ROS) and inflammation levels. The development of rhythmic drugs has become a priority in myocardial IR injury. In this study, resveratrol (RES) and proanthocyanidins (OPC) were utilized to design nanoparticles (NPs), with hyaluronic acid (HA) as the core, grafted with MMP-targeting peptides to improve delivery to injured myocardial regions (HA-RES-OPC-MMP NPs). NPs significantly scavenged ROS, attenuated inflammation, and activated the rhythm gene. Notably, the difference in therapeutic effects on myocardial IR injury in mice at Zeitgeber time (ZT)1 and ZT13 confirms that NPs are rhythm-dependent drugs. At ZT13, echocardiographic and MRI confirm that IR injury in mice was not as severe as at ZT1, yet NPs were also less effective in treatment. Further, Per1/2 knockout mice confirmed the rhythm-dependent treatment of myocardial IR injury by NPs. Molecular studies have shown that rhythmic characteristics of inflammation and Sirt1 transcript levels are the main reasons for the different rhythmic therapeutic effects of NPs. Circadian rhythm-dependent treatment of HA-RES-OPC-MMP NPs has excellent potential for more precise treatment of myocardial IR injury in the future.
期刊介绍:
ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.