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Ultrasound (US)\u2010triggered catalysis offers localized treatment for deep\u2010seated plaques effectively and safely, with demand for targeted delivery and anti\u2010inflammatory properties of sonosensitizers. 2D MXene\u2010based nanomedicine is garnering attention because of their intriguing catalytic properties of scavenging excessive reactive oxygen species (ROS), yet MXene\u2010assisted sonocatalytic therapy (SCT) for treating CVDs remains scarce. Here, this study reports a dual enzyme\u2010mimicking and US\u2010responsive MXene termed Nb\n                    <jats:sub>2<\/jats:sub>\n                    C\u2010Pt@HA\u2010PEG for alleviating atherosclerosis. US irradiation enhances the capability of Nb\n                    <jats:sub>2<\/jats:sub>\n                    C\u2010Pt@HA\u2010PEG nanozymes in eliminating broad\u2010spectrum ROS and resolving vascular inflammation. Besides, actively targeting lesional macrophages improves their systemic delivery to plaque and further boosts anti\u2010atherosclerotic efficacy, contributing to \u224830% plaque size reduction and a more stabilized plaque phenotype. Notably, etching without hydrofluoric acid renders this nanozyme highly biocompatible. In long\u2010term biosafety studies, Nb\n                    <jats:sub>2<\/jats:sub>\n                    C\u2010Pt@HA\u2010PEG is pronouncedly cleared from major organs and no severe changes of liver and kidney functions are observed. Consequently, this work demonstrates that Nb\n                    <jats:sub>2<\/jats:sub>\n                    C\u2010Pt@HA\u2010PEG\u2010mediated SCT effectively ameliorates advanced atherosclerosis without inducing severe cytotoxicity, offering promising translational potential of MXene\u2010based nanomedicine. Besides, it broadens application prospects of MXenes to the biomedical field of treating CVDs.\n                  <\/jats:p>","DOI":"10.1002\/adma.202420189","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T09:50:28Z","timestamp":1751881828000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Plaque\u2010Targeted Delivery of Fluoride\u2010Free MXene Nanozyme for Alleviating Atherosclerosis via Sonocatalytic Therapy"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6698-3324","authenticated-orcid":false,"given":"Qianqian","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Applied Physics The Hong Kong Polytechnic University  Hong Kong 999077 P. R. 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