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Effective noninvasive anti-inflammatory therapies are urgently needed. However, unsatisfactory therapeutic efficacy of current drugs and inadequate drug delivery to the damaged brain are major problems. Nanozymes with robust anti-inflammatory and antioxidative stress properties possess therapeutic possibility for ischemic stroke. However, insufficiency of nanozyme accumulation in the ischemic brain by noninvasive administration hindered their application. Herein, we report a neutrophil-like cell-membrane-coated mesoporous Prussian blue nanozyme (MPBzyme@NCM) to realize noninvasive active-targeting therapy for ischemic stroke by improving the delivery of a nanozyme to the damaged brain based on the innate connection between inflamed brain microvascular endothelial cells and neutrophils after stroke. The long-term in vivo therapeutic efficacy of MPBzyme@NCM for ischemic stroke was illustrated in detail after being delivered into the damaged brain and uptake by microglia. Moreover, the detailed mechanism of ischemic stroke therapy via MPBzyme@NCM uptake by microglia was further studied, including microglia polarization toward M2, reduced recruitment of neutrophils, decreased apoptosis of neurons, and proliferation of neural stem cells, neuronal precursors, and neurons. This strategy may provide an applicative perspective for nanozyme therapy in brain diseases.<\/jats:p>","DOI":"10.1021\/acsnano.0c07973","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T18:48:40Z","timestamp":1610563720000},"page":"2263-2280","source":"Crossref","is-referenced-by-count":359,"title":["Neutrophil-like\nCell-Membrane-Coated Nanozyme Therapy\nfor Ischemic Brain Damage and Long-Term Neurological Functional Recovery"],"prefix":"10.1021","volume":"15","author":[{"given":"Lishuai","family":"Feng","sequence":"first","affiliation":[{"name":"Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital , , ,","place":["Shanghai, People\u2019s Republic of China, 200233"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoran","family":"Dou","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital , , ,","place":["Shanghai, People\u2019s Republic of China, 200233"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuguo","family":"Xia","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital , , ,","place":["Shanghai, People\u2019s Republic of China, 200233"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benhao","family":"Li","sequence":"additional","affiliation":[{"name":"Fudan University , , ,","place":["Shanghai, People\u2019s Republic of China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Fudan University , , ,","place":["Shanghai, People\u2019s Republic of China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Yu","sequence":"additional","affiliation":[{"name":"Fudan University , , ,","place":["Shanghai, People\u2019s Republic of China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1832-8664","authenticated-orcid":true,"given":"Yuanyi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital , , ,","place":["Shanghai, People\u2019s Republic of China, 200233"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Mohamed","family":"El-Toni","sequence":"additional","affiliation":[{"name":"King Saud University , , ,","place":["Riyadh, Saudi Arabia, 11451"]},{"name":"Central Metallurgical Research and Development Institute (CMRDI) , , ,","place":["Helwan, Cairo, Egypt, 11421"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8546-7934","authenticated-orcid":true,"given":"Nada Farouk","family":"Atta","sequence":"additional","affiliation":[{"name":"Cairo University , , , ,","place":["Giza, Cairo, Egypt, 12613"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9097-6725","authenticated-orcid":true,"given":"Ahmed","family":"Galal","sequence":"additional","affiliation":[{"name":"Cairo University , , , ,","place":["Giza, Cairo, Egypt, 12613"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingsheng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital , , ,","place":["Shanghai, People\u2019s Republic of China, 200233"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Cai","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital , , ,","place":["Shanghai, People\u2019s Republic of China, 200233"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital , , ,","place":["Shanghai, People\u2019s Republic of China, 200233"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7886-6144","authenticated-orcid":true,"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fudan University , , ,","place":["Shanghai, People\u2019s Republic of China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"2026081810124483900_cit1","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1016\/S0140-6736(18)31874-9","article-title":"Current\nPractice and Future Directions in the Diagnosis and Acute Treatment\nof Ischaemic 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