Jianyuan Wang, Erwei Xu, Haoran Wang, Ning Ding, Chunlei Liu, Xiaoyu Wang* and Chunzhao Liu*,
{"title":"碳纳米点集成多功能纳米药物在血管-免疫-肌肉系统之间建立再生反馈回路,用于综合治疗危重肢体缺血","authors":"Jianyuan Wang, Erwei Xu, Haoran Wang, Ning Ding, Chunlei Liu, Xiaoyu Wang* and Chunzhao Liu*, ","doi":"10.1021/acsami.5c0136510.1021/acsami.5c01365","DOIUrl":null,"url":null,"abstract":"<p >Critical limb ischemia (CLI) remains a major clinical challenge, with high amputation and mortality rates. Dysregulated intercellular interactions among vascular, immune, and muscle systems in CLI undermine the body’s repair processes. Herein, a multiactive nanomedicine, CDs@Zn@<span>l</span>-Arg, was developed by integrating <i>Panax notoginseng</i> saponin-derived carbon nanodots (CDs-PNS), zinc ions, and <span>l</span>-arginine to induce a mutually supportive cycle of angiogenesis, macrophage reprogramming, and muscle regeneration. CDs-PNS, first identified for their potent antioxidative, angiogenic, and macrophage-reprogramming properties in CLI therapy, are further enhanced by leveraging zeolitic imidazolate frameworks as mediators to physically encapsulate them, while <span>l</span>-arginine is incorporated through electrostatic binding and Schiff base reactions. Individual cell culture experiments demonstrate that, through the integration of various bioactive components, CDs@Zn@<span>l</span>-Arg effectively promotes endothelial tube formation and myosatellite cell proliferation and reduces inflammation and oxidative stress. More importantly, cell coculture models further reveal that CDs@Zn@<span>l</span>-Arg successfully reverses the detrimental intercellular interactions typical of CLI, thereby enhancing the positive crosstalk between endothelial cells, macrophages, and myosatellite cells. In a CLI mouse model, treatment with CDs@Zn@<span>l</span>-Arg significantly improves blood perfusion, reduces inflammation, and accelerates limb function recovery. Altogether, by establishing a regenerative feedback loop among the vascular-immune-muscle system, this multiactive nanomedicine holds promise for overcoming the multifaceted challenges of CLI, providing a breakthrough strategy for integrated therapy.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":"17 17","pages":"24977–24993 24977–24993"},"PeriodicalIF":8.2000,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Carbon Nanodots-Integrated Multifunctional Nanomedicine Establishes a Regenerative Feedback Loop between Vascular-Immune-Muscle Systems for Comprehensive Therapy of Critical Limb Ischemia\",\"authors\":\"Jianyuan Wang, Erwei Xu, Haoran Wang, Ning Ding, Chunlei Liu, Xiaoyu Wang* and Chunzhao Liu*, \",\"doi\":\"10.1021/acsami.5c0136510.1021/acsami.5c01365\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Critical limb ischemia (CLI) remains a major clinical challenge, with high amputation and mortality rates. Dysregulated intercellular interactions among vascular, immune, and muscle systems in CLI undermine the body’s repair processes. Herein, a multiactive nanomedicine, CDs@Zn@<span>l</span>-Arg, was developed by integrating <i>Panax notoginseng</i> saponin-derived carbon nanodots (CDs-PNS), zinc ions, and <span>l</span>-arginine to induce a mutually supportive cycle of angiogenesis, macrophage reprogramming, and muscle regeneration. CDs-PNS, first identified for their potent antioxidative, angiogenic, and macrophage-reprogramming properties in CLI therapy, are further enhanced by leveraging zeolitic imidazolate frameworks as mediators to physically encapsulate them, while <span>l</span>-arginine is incorporated through electrostatic binding and Schiff base reactions. Individual cell culture experiments demonstrate that, through the integration of various bioactive components, CDs@Zn@<span>l</span>-Arg effectively promotes endothelial tube formation and myosatellite cell proliferation and reduces inflammation and oxidative stress. More importantly, cell coculture models further reveal that CDs@Zn@<span>l</span>-Arg successfully reverses the detrimental intercellular interactions typical of CLI, thereby enhancing the positive crosstalk between endothelial cells, macrophages, and myosatellite cells. In a CLI mouse model, treatment with CDs@Zn@<span>l</span>-Arg significantly improves blood perfusion, reduces inflammation, and accelerates limb function recovery. Altogether, by establishing a regenerative feedback loop among the vascular-immune-muscle system, this multiactive nanomedicine holds promise for overcoming the multifaceted challenges of CLI, providing a breakthrough strategy for integrated therapy.</p>\",\"PeriodicalId\":5,\"journal\":{\"name\":\"ACS Applied Materials & Interfaces\",\"volume\":\"17 17\",\"pages\":\"24977–24993 24977–24993\"},\"PeriodicalIF\":8.2000,\"publicationDate\":\"2025-04-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Materials & Interfaces\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acsami.5c01365\",\"RegionNum\":2,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MATERIALS SCIENCE, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Materials & Interfaces","FirstCategoryId":"88","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsami.5c01365","RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
Carbon Nanodots-Integrated Multifunctional Nanomedicine Establishes a Regenerative Feedback Loop between Vascular-Immune-Muscle Systems for Comprehensive Therapy of Critical Limb Ischemia
Critical limb ischemia (CLI) remains a major clinical challenge, with high amputation and mortality rates. Dysregulated intercellular interactions among vascular, immune, and muscle systems in CLI undermine the body’s repair processes. Herein, a multiactive nanomedicine, CDs@Zn@l-Arg, was developed by integrating Panax notoginseng saponin-derived carbon nanodots (CDs-PNS), zinc ions, and l-arginine to induce a mutually supportive cycle of angiogenesis, macrophage reprogramming, and muscle regeneration. CDs-PNS, first identified for their potent antioxidative, angiogenic, and macrophage-reprogramming properties in CLI therapy, are further enhanced by leveraging zeolitic imidazolate frameworks as mediators to physically encapsulate them, while l-arginine is incorporated through electrostatic binding and Schiff base reactions. Individual cell culture experiments demonstrate that, through the integration of various bioactive components, CDs@Zn@l-Arg effectively promotes endothelial tube formation and myosatellite cell proliferation and reduces inflammation and oxidative stress. More importantly, cell coculture models further reveal that CDs@Zn@l-Arg successfully reverses the detrimental intercellular interactions typical of CLI, thereby enhancing the positive crosstalk between endothelial cells, macrophages, and myosatellite cells. In a CLI mouse model, treatment with CDs@Zn@l-Arg significantly improves blood perfusion, reduces inflammation, and accelerates limb function recovery. Altogether, by establishing a regenerative feedback loop among the vascular-immune-muscle system, this multiactive nanomedicine holds promise for overcoming the multifaceted challenges of CLI, providing a breakthrough strategy for integrated therapy.
期刊介绍:
ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.