Abstract
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 Fe(3)O(4)-based poly (lactic-co-glycolic acid) (PLGA) nanoparticles (Fe(3)O(4)@PLGA). Platelet membranes (PM) were extracted through hypotonic lysis, followed by ultrasound-assisted encapsulation onto the surface of Fe(3)O(4)@PLGA, resulting in the formation of PM-coated Fe(3)O(4) nanoparticles (PM/Fe(3)O(4)@PLGA). Characterization of PM/Fe(3)O(4)@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/Fe(3)O(4)@PLGA. In this study, we initially synthesized Fe(3)O(4)@PLGA as the core material. Subsequently, a platelet membrane was employed as a coating for the Fe(3)O(4)@PLGA, aiming to enable the detection of vulnerable atherosclerotic plaques through MRI. In vitro, PM/Fe(3)O(4)@PLGA not only exhibited excellent biosafety but also showed targeted collagen characteristics and MR imaging performance. In vivo, the adhesion of PM/Fe(3)O(4)@PLGA to atherosclerotic lesions was confirmed in a mouse model of vulnerable atherosclerotic plaques. Simultaneously, PM/Fe(3)O(4)@PLGA as a novel contrast agent for MRI has shown effective identification of vulnerable atherosclerotic plaques. In terms of safety profile in vivo, PM/Fe(3)O(4)@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 Fe(3)O(4)@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.