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The aim of this study is to construct a novel erythrocyte membrane\u2010derived nanosystems to reverse endothelial damage in sepsis. Herein, an innovative nanometer calcium metal\u2010organic framework\u00a0(Ca\u2010MOF) is generated for the first time by using chelidonic acid as a ligand and calcium chloride as an ion donor for anti\u2010inflammation. Then, zoliflodacin is loaded into Ca\u2010MOF (CMZ) to sterilize and nanoscale erythrocyte membrane vesicles are prepared by modification with a \u03b33 peptide on the surface (\u03b33\u2010RM) for precise targeting. Finally, \u03b33\u2010RM camouflages the nanocore CMZ, to form novel erythrocyte membrane\u2010camouflaged nanoparticle \u03b33\u2010RCMZ. The superior performance of novel nanosystem results from its suitable biocompatibility, nontoxicity, specific targeting, and anti\u2010inflammatory and bactericidal effects. Its anti\u2010inflammatory mechanism mainly involves inhibiting the Caspase1\u2010nuclear factor kappa\u2010B (Caspase1\u2010NF\u2010\u03baB) pathway and oxidative stress reduction to alleviate endothelial damage. Moreover, the findings have revealed for the first time that the bactericidal drug zoliflodacin also has anti\u2010inflammatory effects in vivo and in vitro. Therefore, the novel nanosystem (\u03b33\u2010RCMZ) provides a new nanotherapy strategy for sepsis treatment.<\/jats:p>","DOI":"10.1002\/adhm.202302320","type":"journal-article","created":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T15:04:00Z","timestamp":1698332640000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["An Erythrocyte Membrane\u2010Derived Nanosystem for Efficient Reversal of Endothelial Injury in Sepsis"],"prefix":"10.1002","volume":"13","author":[{"given":"Yao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Emergency The Third Xiangya Hospital of Central South University  Changsha 410013 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion The Third Xiangya Hospital Central South University  Changsha 410013 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