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Here, ultrasmall iron\u2010gallic acid coordination polymer nanodots (Fe\u2010GA CPNs) were developed as antioxidative neuroprotectors for ischemia stroke therapy guided by PET\/MR imaging. As proven by the electron spin resonance spectrum, the ultrasmall Fe\u2010GA CPNs with ultrasmall size, scavenged ROS efficiently. In vitro experiments revealed that Fe\u2010GA CPNs could protect cell viability after being treated with hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) and displayed the effective elimination of ROS by Fe\u2010GA CPNs, which subsequently restores oxidation balance. When analyzing the middle cerebral artery occlusion model, the neurologic damage displayed by PET\/MR imaging revealed a distinct recovery after treatment with Fe\u2010GA CPNs, which was proved by 2,3,5\u2010triphenyl tetrazolium chloride staining. Furthermore, immunohistochemistry staining indicated that Fe\u2010GA CPNs inhibited apoptosis through protein kinase B (Akt) restoration, whereas western blot and immunofluorescence indicated the activation of the nuclear factor erythroid 2\u2010related factor 2 (Nrf2) and heme oxygenase\u20101 (HO\u20101) pathway following Fe\u2010GA CPNs application. Therefore, Fe\u2010GA CPNs exhibit an impressive antioxidative and neuroprotective role via redox homeostasis recovery by Akt and Nrf2\/HO\u20101 pathway activation, revealing its potential for clinical ischemia stroke treatment.<\/jats:p>","DOI":"10.1002\/exp.20220041","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T16:11:15Z","timestamp":1673971875000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Ultrasmall iron\u2010gallic acid coordination polymer nanodots with antioxidative neuroprotection for PET\/MR imaging\u2010guided ischemia stroke therapy"],"prefix":"10.1002","volume":"3","author":[{"given":"Yujing","family":"Du","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Huo","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Han","sequence":"additional","affiliation":[{"name":"Institute of Functional Nano &amp; Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology Soochow University  Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linqian","family":"Hou","sequence":"additional","affiliation":[{"name":"Institute of Functional Nano &amp; Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology Soochow University  Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bixiao","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Fan","sequence":"additional","affiliation":[{"name":"Departments of Radiology and Medical Physics University of Wisconsin\u2010Madison  Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongkang","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenpeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5324-9094","authenticated-orcid":false,"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Functional Nano &amp; Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology Soochow University  Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4641-0833","authenticated-orcid":false,"given":"Weibo","family":"Cai","sequence":"additional","affiliation":[{"name":"Departments of Radiology and Medical Physics University of Wisconsin\u2010Madison  Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Peking University First Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32152-9"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0b013e31829734f2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-017-1007-y"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1990.00530110107027"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/138945011794182764"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0725-17.2017"},{"key":"e_1_2_9_6_1","first-page":"5556603","volume":"2021","author":"Song X.","year":"2021","journal-title":"Evid. 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