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However, reperfusion causes secondary tissue damage induced by inflammatory responses, called ischemia\/reperfusion (I\/R) injury. Current therapeutic strategies that control inflammation to treat I\/R are less than satisfactory.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report a kind of shield and sword nano-soldier functionalized nanoparticles (monocyte membranes-coated rapamycin nanoparticles, McM\/RNPs) that can reduce inflammation and relieve I\/R injury by blocking monocyte infiltration and inhibiting microglia proliferation. The fabricated McM\/RNPs can actively target and bind to inflammatory endothelial cells, which inhibit the adhesion of monocytes to the endothelium, thus acting as a shield. Subsequently, McM\/RNPs can penetrate the endothelium to reach the injury site, similar to a sword, and release the RAP drug to inhibit the proliferation of inflammatory cells. In a rat I\/R injury model, McM\/RNPs exhibited improved active homing to I\/R injury areas and greatly ameliorated neuroscores and infarct volume. Importantly, in vivo animal studies revealed good safety for McM\/RNPs treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results demonstrated that the developed McM\/RNPs may serve as an effective and safe nanovehicles for I\/R injury therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Graphic abstract<\/jats:title><\/jats:sec>","DOI":"10.1186\/s12951-021-01067-0","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T10:05:04Z","timestamp":1634810704000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Functionalized nanoparticles with monocyte membranes and rapamycin achieve synergistic chemoimmunotherapy for reperfusion-induced injury in ischemic stroke"],"prefix":"10.1186","volume":"19","author":[{"given":"Yanyun","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiping","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhui","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiliang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guixue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,21]]},"reference":[{"key":"1067_CR1","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1038\/s41572-019-0118-8","volume":"5","author":"BCV Campbell","year":"2019","unstructured":"Campbell BCV, et al. 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