{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T21:18:28Z","timestamp":1793654308160,"version":"4.5.1"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Atherosclerosis (AS) is a primary cause of cardiovascular disease and significantly contributes to the global disease burden. Empagliflozin (EMP), a candidate drug for AS treatment, has not been clinically approved due to challenges including poor solubility, low bioavailability, and potential toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To address these challenges, we constructed a platelet membrane-biomimetic, mitochondria-targeted delivery system (PM@EPPT). This system was developed by loading EMP into PCL-PEG polymeric micelle, modifying the PEG terminus with triphenylphosphine (TPP), and coating the nanoparticle surface with platelet membranes. We then evaluated its efficacy against AS using both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The PM@EPPT system exhibited favorable physical properties and biocompatibility. <jats:italic>In vitro<\/jats:italic>, it alleviated oxidative stress-induced macrophage apoptosis by scavenging reactive oxygen species (ROS), restoring mitochondrial membrane potential, and activating mitophagy. In ApoE<jats:sup>-\/-<\/jats:sup> mouse models, PM@EPPT significantly reduced aortic plaque area by 43%, decreased the expression of inflammatory markers (CD68 and MMP-9), increased levels of the plaque stability marker (\u03b1-SMA), and improved lipid profiles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In conclusion, PM@EPPT enhances EMP bioavailability through platelet membrane-mediated arterial plaque targeting and TPP-modified mitochondrial targeting. This study provides experimental evidence for optimizing EMP efficacy in AS treatment and developing therapeutic platforms for other poorly soluble drugs targeting AS.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fbioe.2025.1638034","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T05:26:53Z","timestamp":1757309213000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Platelet-mitochondria dual-targeted nanocarriers for enhanced empagliflozin therapy in atherosclerosis"],"prefix":"10.3389","volume":"13","author":[{"given":"Yue","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiaoJin","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"13707","DOI":"10.3389\/bjbs.2024.13707","article-title":"Pioneering advances and innovative applications of mesoporous carriers for mitochondria-targeted therapeutics","volume":"81","author":"Al Tahan","year":"2024","journal-title":"Br. 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