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Proinflammatory M1 macrophage is reported to aggravate sympathetic overactivation and cause VAs. Therefore, the depletion of M1 macrophage is anticipated to inhibit LSG overactivation and alleviate MI\u2010induced VAs. Herein, oxygen\u2010independent photodynamic therapy (Oi\u2010PDT) combined with M1 macrophage targeting is applied to selectively deplete M1 macrophage in LSG and further treat MI\u2010induced VAs. Oi\u2010PDT, which overcomes the limitation of extremely dependence on oxygen content in traditional PDT, is constructed through the generation of oxidizing photogenerated holes (h<jats:sup>+<\/jats:sup>) under the irradiation of near\u2010infrared (NIR) light on the prepared Oi\u2010PDT agent (PPSCD). Meanwhile, PPSCD targets M1 macrophage through conjunction with SR\u2010A receptor. The selective consumption of M1 macrophage is attributed to both apoptosis and ferroptosis induced by h<jats:sup>+<\/jats:sup>, <jats:sup>1<\/jats:sup>O<jats:sub>2<\/jats:sub>, and O<jats:sub>2<\/jats:sub><jats:sup>\u2022\u2212<\/jats:sup> generated in Oi\u2010PDT. In vivo tests indicated neural activity experienced a notable reduction from 104.5 \u00b1\u00a0 2.9 to 51.5 \u00b1\u00a06.7 after MI with Oi\u2010PDT treatment, thereby significantly inhibited VAs. The implementation of this study provides a promising strategy for selective consumption of M1 macrophages and treatment of VAs induced by MI.<\/jats:p>","DOI":"10.1002\/smll.202409244","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T09:15:17Z","timestamp":1734945317000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Oxygen\u2010Independent Photodynamic Therapy\u2010Mediated Selective Consumption of M1 Macrophage Against Ventricular Arrhythmias via Sympathetic Neuromodulation"],"prefix":"10.1002","volume":"21","author":[{"given":"Heng","family":"Lin","sequence":"first","affiliation":[{"name":"Cardiovascular Hospital Renmin Hospital of Wuhan University Hubei Key Laboratory of Autonomic Nervous System Modulation Cardiac Autonomic Nervous System Research Center of Wuhan University  Wuhan 430060 P. R. 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