Atherosclerosis is the most recognized pathological basis of cardiovascular disease, and the rupture of vulnerable atherosclerotic plaque is one of the most important factors leading to the end-stage event, myocardial infarction. Nanomedicine has emerged as a stratedgy to improve the diagnositic and therapeutic efficacy. The microenvironment has attracted great interest as the target of an intelligent drug delivery system to alter the pathological process. This review summarizes microenvironment-targeted nanomedicine for diagnosis and treatment of atherosclerosis. The pathological processes share similar characteristics of microenvironment, including high endogenous reactive oxygen species levels, acidic pH values, and high enzyme activity. Target cell population may include endothelial cells, vascular smooth muscle cells, macrophages, and foam cells. Lesion neovascularization also represents a potent target. Nanomaterials have been applied in fluorescence imaging, magnetic resonance imaging, single-photon emission computed tomography/computed tomography imaging, and multimodal imaging for detecting atherosclerosis. The nanomaterial-based treatment approaches of atherosclerosis include microRNA-based therapy, photodynamic therapy, anti-inflammatory therapy, antioxidant therapy, and immunotherapy. Although nanomedicine expanded a promising avenue for more detailed diagnosis procedure and efficient treatment of atherosclerosis, the biosafety concerns still remain awaiting further investigation. The clinical application of microenvironment-targeted nanomedicine in atherosclerosis still represents a challenge.
Impact Statement
This review highlights the revolutionary potential of microenvironment-targeted nanomedicine in the fight against this pervasive condition, emphasizing the shared characteristics of the atherosclerotic microenvironment—such as elevated reactive oxygen species, acidic pH, and elevated enzyme activity—as key targets for advanced drug delivery systems. Through the application in imaging techniques along with targeted therapies including photodynamic, anti-inflammatory, antioxidant, and immunotherapies, nanomedicine offers a comprehensive, multifaceted approach to both detecting and treating atherosclerosis. This review underscores the urgent need for continued research to ensure safe and effective use, ultimately paving the way for more personalized and targeted therapies that could transform patient outcomes.
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