How Advanced is Nanomedicine to Treat Atherosclerosis? A Comprehensive Review of the Literature

Jiahui Zhang,1– 3,* Junran Tong,1– 3,* Yang Sun,4,* Jinpeng Sun,1– 3 Ran Gao,1– 3 Di Sun,5 Xiaopeng Guo,6 Yumiao Wei1– 3 1Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 4Department of Medical Records Management and Statistics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 5Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 6Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yumiao Wei, Email Ymwei12@sina.com Xiaopeng Guo, Email guoxiaopenghe@163.comAbstract: Atherosclerosis (AS) is a major underlying cause of cardiovascular disease. Rupture of unstable atherosclerotic plaques can induce severe acute cardiovascular events and sudden cardiac death. Therefore, developing targeted interventional therapies for atherosclerotic plaques is clinically important to improve cardiovascular mortality. With the advancement of nanomedicine, nanomaterials have demonstrated great potential in atherosclerosis treatment due to their unique compositional/structural features, synthesis strategies, and surface modifications. Based on the pathological characteristics of atherosclerotic plaques, the design and preparation of stimulus-responsive, surface-functionalized, and conditionally-released nanomaterials have become an important approach to achieving precise intervention for atherosclerotic lesions. Considering the pathological features of different cell types involved in AS progression, this review describes the targeting strategies, structural and functional designs, and potential mechanisms of action of targeted nanotherapies in the treatment of atherosclerosis. By summarizing representative recent studies in detail, we reveal the intrinsic interactions and relationships between current targeted nanotherapies and atherosclerotic plaques. Finally, this review provides an outlook on the future application of nanomaterials by presenting key scientific questions that have not yet been addressed, to advance the clinical translation of targeted nanotherapies for atherosclerosis. The diagram illustrates a process involving nanomedicine design and surface modification for targeted cellular intervention. The input section includes micelles, liposomes, PMM-core/PEG-shell, Au, antibody and peptides. These components are used in a process targeting key atherosclerotic cells such as endothelial cells (ECs), macrophages and vascular smooth muscle cells (VSMCs). The output is plaque stabilization or regression, leading to clinical translation and patient recovery. The flow from input to output is depicted with arrows, showing the progression from nanomedicine design to targeted delivery and eventual patient recovery.Diagram of nanomedicine design for targeted delivery to atherosclerotic cells, leading to plaque stabilization and patient recovery.Keywords: atherosclerosis, nanomaterials, targeted therapies