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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Atherosclerosis (AS) is a lipid-driven chronic inflammatory disease and the principal pathological basis of coronary artery disease, ischemic stroke, and peripheral artery disease. Despite advances in lipid-lowering, antiplatelet, anti-inflammatory, and revascularization strategies, current treatments do not selectively modulate the heterogeneous cellular and inflammatory microenvironments within individual plaques. Cell membrane-coated nanoparticles (CMNs) have therefore emerged as biomimetic delivery platforms that combine the functional versatility of synthetic nanocores with selected biological properties of donor-cell membranes. This review summarizes the fabrication of CMNs and critically compares platelet-, macrophage-, neutrophil-, monocyte-, erythrocyte-, and hybrid membrane-coated nanoplatforms, together with emerging T-cell-targeted nanotherapeutic strategies. Particular attention is given to membrane-source selection, receptor\u2013ligand interactions, immune evasion, lesion-directed accumulation, stimulus-responsive cargo release, and the modulation of inflammation, oxidative stress, lipid metabolism, and defective efferocytosis. We further discuss major translational barriers, including donor- and activation-state-dependent membrane heterogeneity, incomplete or unstable coating, manufacturing reproducibility, scalability, thrombogenicity, immunogenicity, and the limited predictive value of short-term small-animal models. A pathology-matched and minimum-sufficient-complexity framework is proposed to guide the rational development of safer, more reproducible, and clinically relevant biomimetic nanotherapies for AS.<\/jats:p>","DOI":"10.3390\/ijms27177718","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"7718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cell Membrane-Coated Biomimetic Nanocarriers for Plaque-Targeted Atherosclerosis Therapy: Molecular Mechanisms, Inflammatory Microenvironments, and Translational Challenges"],"prefix":"10.3390","volume":"27","author":[{"given":"Ruiyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Key Laboratory of Biological Targeted Therapy (Huazhong University of Science and Technology), Ministry of Education, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xujing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Key Laboratory of Biological Targeted Therapy (Huazhong University of Science and Technology), Ministry of Education, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5350-6033","authenticated-orcid":false,"given":"Jinpeng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Key Laboratory of Biological Targeted Therapy (Huazhong University of Science and Technology), Ministry of Education, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumiao","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Key Laboratory of Biological Targeted Therapy (Huazhong University of Science and Technology), Ministry of Education, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/j.clinthera.2023.09.020","article-title":"Global Trends in Atherosclerotic Cardiovascular Disease","volume":"45","author":"Nedkoff","year":"2023","journal-title":"Clin. 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