Li Yuyu, Wang Yujie, Xia Zequn, Xie Yangjing, Ke Daozheng, Song Bing, Mu Dan, Yu Ronghui, Xie Jun
Department of Cardiology National Cardiovascular Disease Regional Center for Anhui the First Affiliated Hospital of Anhui Medical University Hefei China.
Beijing Institute of Heart, Lung, and Blood Vessel Diseases Beijing Anzhen Hospital Affiliated to Capital Medical University Beijing China.
Smart Med. 2024 Jun 4;3(2):e20240006. doi: 10.1002/SMMD.20240006. eCollection 2024 Jun.
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 FeO-based poly (lactic-co-glycolic acid) (PLGA) nanoparticles (FeO@PLGA). Platelet membranes (PM) were extracted through hypotonic lysis, followed by ultrasound-assisted encapsulation onto the surface of FeO@PLGA, resulting in the formation of PM-coated FeO nanoparticles (PM/FeO@PLGA). Characterization of PM/FeO@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/FeO@PLGA. In this study, we initially synthesized FeO@PLGA as the core material. Subsequently, a platelet membrane was employed as a coating for the FeO@PLGA, aiming to enable the detection of vulnerable atherosclerotic plaques through MRI. In vitro, PM/FeO@PLGA not only exhibited excellent biosafety but also showed targeted collagen characteristics and MR imaging performance. In vivo, the adhesion of PM/FeO@PLGA to atherosclerotic lesions was confirmed in a mouse model of vulnerable atherosclerotic plaques. Simultaneously, PM/FeO@PLGA as a novel contrast agent for MRI has shown effective identification of vulnerable atherosclerotic plaques. In terms of safety profile in vivo, PM/FeO@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 FeO@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.
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生率具有至关重要的临床意义。然而，在遍布全身循环的弥漫性动脉粥样硬化斑块中识别易损斑块在临床实践中仍然是一项重大挑战。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FeO的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒（FeO@PLGA）。通过低渗裂解提取血小板膜（PM），然后通过超声辅助将其包裹在FeO@PLGA表面，从而形成PM包被的FeO纳米颗粒（PM/FeO@PLGA）。对PM/FeO@PLGA的表征涉及使用动态光散射、透射电子显微镜、蛋白质免疫印迹和磁共振成像（MRI）。通过对载脂蛋白E基因敲除（ApoE）小鼠进行颈动脉缩窄和高脂饮食构建动脉粥样硬化易损斑块模型。采用免疫荧光和MRI技术验证PM/FeO@PLGA的功能。在本研究中，我们首先合成了FeO@PLGA作为核心材料。随后，采用血小板膜作为FeO@PLGA的涂层，旨在通过MRI实现对易损动脉粥样硬化斑块的检测。在体外，PM/FeO@PLGA不仅表现出优异的生物安全性，还表现出靶向胶原特性和MR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/FeO@PLGA对动脉粥样硬化病变的粘附。同时，PM/FeO@PLGA作为一种新型的MRI造影剂已显示出对易损动脉粥样硬化斑块的有效识别。就体内安全性而言，PM/FeO@PLGA在血液中未表现出明显的器官毒性或炎症反应。在本研究中，我们成功开发了一种血小板膜包被的纳米颗粒系统，用于将FeO@PLGA靶向递送至易损动脉粥样硬化斑块。这种创新系统允许使用MRI对易损斑块进行可视化，从而证明其在增强易损动脉粥样硬化斑块临床诊断方面的潜力。
