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To overcome the inherent limitations of conventional oral agents and nanocarrier-based systems, we developed a macrophage-targeted modulator by integrating curcumin (Cur) with gold nanoparticles (AuNPs). This construct was designed to concurrently correct dysregulated lipid homeostasis and suppress the expansion of pro-inflammatory macrophage populations. Specifically, protoporphyrin (Por) as a \u03c0-conjugated moiety was conjugated to polycaprolactone (PCL) via reactive oxygen species (ROS)-cleavable thioketal (TK) linkers, while AuNPs were functionalized onto hyaluronic acid (HA) backbones (HAPPT) to enable CD44-mediated foam cell recognition. Through self-assembly, Cur was efficiently loaded into the nano-system to yield the final modulator, Cur@HAPPT. Upon cellular uptake, Cur@HAPPT not only drove M1-to-M2 phenotypic repolarization but also provoked robust autophagic activation, collectively contributing to inflammation resolution. The autophagy-triggered cascade further facilitated lipid efflux and constrained inflammatory macrophage expansion, thereby producing a synergistic therapeutic benefit. Overall, Cur@HAPPT effectively attenuated AS progression and reinforced plaque stability, positioning this polymeric modulator as a promising targeted intervention for AS management.<\/jats:p>","DOI":"10.1021\/acsabm.6c00847","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:37:48Z","timestamp":1784565468000},"page":"7114-7129","source":"Crossref","is-referenced-by-count":0,"title":["A Multifunctional Polymeric Modulator Targeting Autophagic Lipid Efflux for Efficient Atherosclerosis Therapy"],"prefix":"10.1021","volume":"9","author":[{"given":"Tengfei","family":"Yu","sequence":"first","affiliation":[{"name":"The Affiliated Hospital of Qingdao University , , ,","place":["Qingdao, China, 266003"]},{"name":"Qingdao University , , ,","place":["Qingdao, China, 266073"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dahai","family":"Yu","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266073"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Xu","sequence":"additional","affiliation":[{"name":"Qingdao Central Hospital, University of Health and Rehabilitation Sciences , , ,","place":["Qingdao, China, 266000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Yang","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266073"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0510-420X","authenticated-orcid":true,"given":"Long","family":"Xu","sequence":"additional","affiliation":[{"name":"Ningbo University , , ,","place":["Ningbo, China, 315211"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0939-9869","authenticated-orcid":true,"given":"Bin","family":"He","sequence":"additional","affiliation":[{"name":"Sichuan University , , ,","place":["Chengdu, China, 610064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Sun","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266073"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1084-6117","authenticated-orcid":true,"given":"Yan","family":"Liang","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266073"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujie","family":"Wang","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University , , ,","place":["Qingdao, China, 266003"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"issue":"11","key":"2026080308063046900_cit1","doi-asserted-by":"publisher","first-page":"e275","DOI":"10.1161\/ATVBAHA.120.314735","article-title":"Lymphatics in Cardiovascular Disease","volume":"40","author":"Zhou","year":"2020","journal-title":"Arterioscler., Thromb., Vasc. 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