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Developing targeted TH strategies still remains a problem. In this work, a near infrared emissive, ischemic targeted nanocomposite is demonstrated to achieve localized TH at the ischemic\u2010reperfusion site. Rare earth doped nanoparticle as the core of the nanocomposite generates near infrared II luminescence for the guidance of delivery process. 2H,3H\u2010decafluoropentane and ammonium nitrate loaded in the mesoporous silica layer of the nanocomposite serve as physical and chemical cooling agents for temperature reduction in the brain. Surface ligands modified with stroke\u2010homing peptide and reactive oxygen species cleavable ketone moieties of the nanocomposite can target the inflammatory ischemic region and the promote cooling effects. By the intranasal administration of the nanocomposite in ischemic stroke mice model, infract area and pro\u2010inflammatory factors levels of the brain are effectively reduced and the neurological functions are preserved. This work points to a concept of localized hypothermia method via nanomaterials, which may inspire the development of TH therapy for stroke in the future.<\/jats:p>","DOI":"10.1002\/smll.202505141","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T11:40:20Z","timestamp":1754653220000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["NIR\u2010II Emissive, Ischemia Targeted Nanocomposites for Localized Therapeutic Hypothermia of Cerebral Ischemia\u2010Reperfusion Injury"],"prefix":"10.1002","volume":"21","author":[{"given":"Pengrui","family":"Wang","sequence":"first","affiliation":[{"name":"School of Physical Science and Technology &amp; State Key Laboratory of Advanced Medical Materials and Devices ShanghaiTech University  393 Middle Huaxia, Road Shanghai 201210 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