无创血小板膜包裹的 Fe3O4 纳米粒子可识别易受损伤的动脉粥样硬化斑块

Yuyu Li, Yujie Wang, Zequn Xia, Yangjing Xie, Daozheng Ke, Bing Song, Dan Mu, Ronghui Yu, Jun Xie
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引用次数: 0

摘要

易损动脉粥样硬化斑块是致命性心脑血管疾病的主要病理基础。准确识别和治疗这些易损斑块对于降低心肌梗死和中风的发病率具有极其重要的临床意义。然而,如何识别分散在全身循环中的弥漫性动脉粥样硬化斑块中的易损斑块仍然是临床实践中的一大挑战。研究人员采用双乳液溶剂蒸发法,特别是水包油包水(W/O/W)技术,制备了基于Fe3O4的聚(乳酸-共聚乙醇酸)(PLGA)纳米颗粒(Fe3O4@PLGA)。通过低渗裂解提取血小板膜(PM),然后在超声辅助下将其封装到Fe3O4@PLGA表面,形成PM包覆的Fe3O4纳米颗粒(PM/Fe3O4@PLGA)。对 PM/Fe3O4@PLGA 的表征包括使用动态光散射、透射电子显微镜、Western 印迹和磁共振成像(MRI)。通过颈动脉闭塞和载脂蛋白E-/-(载脂蛋白E基因敲除)小鼠的高脂饮食,构建了动脉粥样硬化脆弱斑块模型。采用免疫荧光和磁共振成像技术验证了 PM/Fe3O4@PLGA 的功能。在这项研究中,我们首先合成了 Fe3O4@PLGA 作为核心材料。随后,我们采用血小板膜作为 Fe3O4@PLGA 的涂层,旨在通过核磁共振成像检测易损的动脉粥样硬化斑块。在体外,PM/Fe3O4@PLGA 不仅具有良好的生物安全性,而且还显示出靶向胶原蛋白特性和磁共振成像性能。在体内,在易损动脉粥样硬化斑块小鼠模型中证实了 PM/Fe3O4@PLGA 与动脉粥样硬化病变的粘附性。同时,PM/Fe3O4@PLGA 作为一种新型核磁共振成像造影剂,能有效识别易损的动脉粥样硬化斑块。就体内安全性而言,PM/Fe3O4@PLGA 未显示出明显的器官毒性或血液中的炎症反应。在本研究中,我们成功开发了一种血小板-膜包被纳米粒子系统,用于将 Fe3O4@PLGA 靶向输送到易损动脉粥样硬化斑块。这种创新的系统可以利用核磁共振成像对易损斑块进行可视化,从而证明了它在提高易损动脉粥样硬化斑块临床诊断方面的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Noninvasive platelet membrane‐coated Fe3O4 nanoparticles identify vulnerable atherosclerotic plaques
Vulnerable atherosclerotic plaques serve as the primary pathological basis for fatal cardiovascular and cerebrovascular diseases. The precise identification and treatment of these vulnerable plaques hold paramount clinical importance in mitigating the incidence of myocardial infarction and stroke. Nevertheless, the identification of vulnerable plaques within the diffuse atherosclerotic plaques dispersed throughout the systemic circulation continues to pose a substantial challenge in clinical practice. Double emulsion solvent evaporation method, specifically the water‐in‐oil‐in‐water (W/O/W) technique, was employed to fabricate Fe3O4‐based poly (lactic‐co‐glycolic acid) (PLGA) nanoparticles (Fe3O4@PLGA). Platelet membranes (PM) were extracted through hypotonic lysis, followed by ultrasound‐assisted encapsulation onto the surface of Fe3O4@PLGA, resulting in the formation of PM‐coated Fe3O4 nanoparticles (PM/Fe3O4@PLGA). Characterization of PM/Fe3O4@PLGA involved the use of dynamic light scattering, transmission electron microscopy, western blotting, and magnetic resonance imaging (MRI). A model of atherosclerotic vulnerable plaques was constructed by carotid artery coarctation and a high‐fat diet fed to ApoE−/− (Apolipoprotein E knockout) mice. Immunofluorescence and MRI techniques were employed to verify the functionality of PM/Fe3O4@PLGA. In this study, we initially synthesized Fe3O4@PLGA as the core material. Subsequently, a platelet membrane was employed as a coating for the Fe3O4@PLGA, aiming to enable the detection of vulnerable atherosclerotic plaques through MRI. In vitro, PM/Fe3O4@PLGA not only exhibited excellent biosafety but also showed targeted collagen characteristics and MR imaging performance. In vivo, the adhesion of PM/Fe3O4@PLGA to atherosclerotic lesions was confirmed in a mouse model of vulnerable atherosclerotic plaques. Simultaneously, PM/Fe3O4@PLGA as a novel contrast agent for MRI has shown effective identification of vulnerable atherosclerotic plaques. In terms of safety profile in vivo, PM/Fe3O4@PLGA has not demonstrated significant organ toxicity or inflammatory response in the bloodstream. In this study, we successfully developed a platelet‐membrane‐coated nanoparticle system for the targeted delivery of Fe3O4@PLGA to vulnerable atherosclerotic plaques. This innovative system allows for the visualization of vulnerable plaques using MRI, thereby demonstrating its potential for enhancing the clinical diagnosis of vulnerable atherosclerotic plaques.
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