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Targeting myocardial ferroptosis through the chelation of excess iron has therapeutic potential for MI treatment. However, iron chelation in post ischemic injury areas using conventional iron\u2010specific chelators is hindered by ineffective myocardial intracellular chelation, rapid clearance, and high systemic toxicity. A chitosan\u2010desferrioxamine nanosponge (CDNS) is designed by co\u2010crosslinking chitosan and deferoxamine through noncovalent gelation to address these challenges. This architecture facilitates direct iron chelation regardless of deferoxamine (DFO) release due to its sponge\u2010like porous hydrogel structure. Upon cellular internalization, CDNS can effectively chelate cellular iron and facilitate the efflux of captured iron, thereby inhibiting ferroptosis and associated oxidative stress and lipid peroxidation. In MI mouse models, myocardial injection of CDNS promotes sustainable retention and the suppression of ferroptosis in the infarcted heart. This intervention improves cardiac function and alleviates adverse cardiac remodeling post\u2010MI, leading to decreased oxidative stress and the promotion of angiogenesis due to ferroptosis inhibition by CDNS in the infarcted heart. This study reveals a nanosponge\u2010based nanomedicine targeting myocardial ferroptosis with efficient iron chelation and efflux, offering a promising MI treatment.<\/jats:p>","DOI":"10.1002\/advs.202305895","type":"journal-article","created":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:39:47Z","timestamp":1714178387000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Nanosponge for Iron Chelation and Efflux: A Ferroptosis\u2010Inhibiting Approach for Myocardial Infarction Therapy"],"prefix":"10.1002","volume":"11","author":[{"given":"Qingbo","family":"Lv","sequence":"first","affiliation":[{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province Department of Cardiology Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou 310016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province Department of Cardiology Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou 310016 China"},{"name":"Department of Cardiovascular Surgery Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province Department of Cardiology Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou 310016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boxuan","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province Department of Cardiology Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou 310016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wujiao","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province Department of Cardiology Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou 310016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawen","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province Department of Cardiology Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou 310016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihui","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province Department of Cardiology Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou 310016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Qiushi Academy for Advanced Studies Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guosheng","family":"Fu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province Department of Cardiology Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou 310016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7612-3567","authenticated-orcid":false,"given":"Yun","family":"Xiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province Department of Cardiology Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou 310016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,26]]},"reference":[{"key":"e_1_2_8_1_1","first-page":"9349","volume":"12","author":"Khan M. 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