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。

IF 8.3 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY
Small Science Pub Date : 2025-07-06 eCollection Date: 2025-09-01 DOI:10.1002/smsc.202500221
Ximei Dai, Zhiyue Wang, Jiaqi Lu, Yutong Xu, Xingji Liu, Jianchen Qi, Tao Zheng, Feng Wang, Guangming Lu, Longjiang Zhang, Jie Sheng, Guifen Yang
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引用次数: 0

摘要

动脉粥样硬化(AS)是心血管事件的重要诱因。最近的研究表明,泡沫细胞的铁下垂是AS的一个重要驱动因素。然而,对精确的抗铁下垂疗法的见解仍然有限。本研究通过将叶酸修饰的聚多巴胺(PDA)纳米粒子(NPs)与l -精氨酸(FPLG)偶联来设计多功能治疗纳米平台,以抑制泡沫细胞的铁凋亡。体外研究表明,FPLG NPs通过清除活性氧、上调GPX4和NRF2活性、调节脂质代谢,有效减轻氧化低密度脂蛋白(ox-LDL)刺激的巨噬细胞中的铁凋亡。在体内,荧光成像和无螯合剂68ga标记的正电子发射断层扫描/计算机断层扫描(PET/CT)证实,FPLG NPs通过叶酸受体(FRs)介导的靶向和增强的渗透性和滞留效应(EPR效应)在动脉粥样硬化斑块中表现出优先积累。在ApoE-/-小鼠中使用FPLG NPs治疗可减少斑块面积40%以上,增强纤维帽稳定性,并减轻铁下垂。转录组学进一步揭示,FPLG治疗抑制铁下垂和炎症途径。这种双模平台集成了有针对性的铁下垂抑制和实时成像,为精确的AS管理提供了有前途的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Positron Emission Tomography/Computed Tomography Imaging-Guided Polydopamine Nanoparticles Attenuate Foam Cell Ferroptosis for Targeted Antiatherosclerotic Therapy.

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.

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来源期刊
CiteScore
14.00
自引率
2.40%
发文量
0
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.
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