Ximei Dai, Zhiyue Wang, Jiaqi Lu, Yutong Xu, Xingji Liu, Jianchen Qi, Tao Zheng, Feng Wang, Guangming Lu, Longjiang Zhang, Jie Sheng, Guifen Yang
{"title":"正电子发射断层扫描/计算机断层扫描成像引导的聚多巴胺纳米颗粒减轻泡沫细胞铁下垂用于靶向抗动脉粥样硬化治疗。","authors":"Ximei Dai, Zhiyue Wang, Jiaqi Lu, Yutong Xu, Xingji Liu, Jianchen Qi, Tao Zheng, Feng Wang, Guangming Lu, Longjiang Zhang, Jie Sheng, Guifen Yang","doi":"10.1002/smsc.202500221","DOIUrl":null,"url":null,"abstract":"<p><p>Atherosclerosis (AS) is a significant contributor to cardiovascular events. Recent studies have demonstrated that ferroptosis of foam cells is a significant driver of AS. Nevertheless, insights into the precise antiferroptosis therapies remain limited. Here, a multifunctional theranostic nanoplatform is engineered by conjugating folate-modified polydopamine (PDA) nanoparticles (NPs) with L-arginine (FPLG) to inhibit ferroptosis of foam cells. In vitro studies demonstrate that FPLG NPs effectively attenuate ferroptosis in oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages by scavenging reactive oxygen species, upregulating GPX4 and NRF2 activity, and regulating lipid metabolism. In vivo, FPLG NPs exhibit preferential accumulation in atherosclerotic plaques via folate receptors (FRs)-mediated targeting and the enhanced permeability and retention effect (EPR effect), as confirmed by fluorescence imaging and chelator-free <sup>68</sup>Ga-labeled positron emission tomography/computed tomography (PET/CT). Treatment with FPLG NPs in ApoE<sup>-/-</sup> mice reduces plaque area by over 40%, enhances fibrous cap stability, and mitigates ferroptosis. Transcriptomics further reveals that the FPLG treatment suppresses ferroptosis and inflammatory pathways. This dual-modality platform integrates targeted ferroptosis inhibition and real-time imaging, offering a promising strategy for precise AS management.</p>","PeriodicalId":29791,"journal":{"name":"Small Science","volume":"5 9","pages":"2500221"},"PeriodicalIF":8.3000,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12412604/pdf/","citationCount":"0","resultStr":"{\"title\":\"Positron Emission Tomography/Computed Tomography Imaging-Guided Polydopamine Nanoparticles Attenuate Foam Cell Ferroptosis for Targeted Antiatherosclerotic Therapy.\",\"authors\":\"Ximei Dai, Zhiyue Wang, Jiaqi Lu, Yutong Xu, Xingji Liu, Jianchen Qi, Tao Zheng, Feng Wang, Guangming Lu, Longjiang Zhang, Jie Sheng, Guifen Yang\",\"doi\":\"10.1002/smsc.202500221\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Atherosclerosis (AS) is a significant contributor to cardiovascular events. Recent studies have demonstrated that ferroptosis of foam cells is a significant driver of AS. Nevertheless, insights into the precise antiferroptosis therapies remain limited. Here, a multifunctional theranostic nanoplatform is engineered by conjugating folate-modified polydopamine (PDA) nanoparticles (NPs) with L-arginine (FPLG) to inhibit ferroptosis of foam cells. In vitro studies demonstrate that FPLG NPs effectively attenuate ferroptosis in oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages by scavenging reactive oxygen species, upregulating GPX4 and NRF2 activity, and regulating lipid metabolism. In vivo, FPLG NPs exhibit preferential accumulation in atherosclerotic plaques via folate receptors (FRs)-mediated targeting and the enhanced permeability and retention effect (EPR effect), as confirmed by fluorescence imaging and chelator-free <sup>68</sup>Ga-labeled positron emission tomography/computed tomography (PET/CT). Treatment with FPLG NPs in ApoE<sup>-/-</sup> mice reduces plaque area by over 40%, enhances fibrous cap stability, and mitigates ferroptosis. Transcriptomics further reveals that the FPLG treatment suppresses ferroptosis and inflammatory pathways. This dual-modality platform integrates targeted ferroptosis inhibition and real-time imaging, offering a promising strategy for precise AS management.</p>\",\"PeriodicalId\":29791,\"journal\":{\"name\":\"Small Science\",\"volume\":\"5 9\",\"pages\":\"2500221\"},\"PeriodicalIF\":8.3000,\"publicationDate\":\"2025-07-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12412604/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Small Science\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/smsc.202500221\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/9/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MATERIALS SCIENCE, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Small Science","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/smsc.202500221","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
Atherosclerosis (AS) is a significant contributor to cardiovascular events. Recent studies have demonstrated that ferroptosis of foam cells is a significant driver of AS. Nevertheless, insights into the precise antiferroptosis therapies remain limited. Here, a multifunctional theranostic nanoplatform is engineered by conjugating folate-modified polydopamine (PDA) nanoparticles (NPs) with L-arginine (FPLG) to inhibit ferroptosis of foam cells. In vitro studies demonstrate that FPLG NPs effectively attenuate ferroptosis in oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages by scavenging reactive oxygen species, upregulating GPX4 and NRF2 activity, and regulating lipid metabolism. In vivo, FPLG NPs exhibit preferential accumulation in atherosclerotic plaques via folate receptors (FRs)-mediated targeting and the enhanced permeability and retention effect (EPR effect), as confirmed by fluorescence imaging and chelator-free 68Ga-labeled positron emission tomography/computed tomography (PET/CT). Treatment with FPLG NPs in ApoE-/- mice reduces plaque area by over 40%, enhances fibrous cap stability, and mitigates ferroptosis. Transcriptomics further reveals that the FPLG treatment suppresses ferroptosis and inflammatory pathways. This dual-modality platform integrates targeted ferroptosis inhibition and real-time imaging, offering a promising strategy for precise AS management.
期刊介绍:
Small Science is a premium multidisciplinary open access journal dedicated to publishing impactful research from all areas of nanoscience and nanotechnology. It features interdisciplinary original research and focused review articles on relevant topics. The journal covers design, characterization, mechanism, technology, and application of micro-/nanoscale structures and systems in various fields including physics, chemistry, materials science, engineering, environmental science, life science, biology, and medicine. It welcomes innovative interdisciplinary research and its readership includes professionals from academia and industry in fields such as chemistry, physics, materials science, biology, engineering, and environmental and analytical science. Small Science is indexed and abstracted in CAS, DOAJ, Clarivate Analytics, ProQuest Central, Publicly Available Content Database, Science Database, SCOPUS, and Web of Science.