An Erythrocyte Membrane‐Derived Nanosystem for Efficient Reversal of Endothelial Injury in Sepsis

Abstract Sepsis is caused by a disordered host immune in response to infection and endothelial cells perform a crucial role in boosting immunity reaction in the pathophysiology of sepsis and septic organ failure. The aim of this study is to construct a novel erythrocyte membrane‐derived nanosystems to reverse endothelial damage in sepsis. Herein, an innovative nanometer calcium metal‐organic framework (Ca‐MOF) is generated for the first time by using chelidonic acid as a ligand and calcium chloride as an ion donor for anti‐inflammation. Then, zoliflodacin is loaded into Ca‐MOF (CMZ) to sterilize and nanoscale erythrocyte membrane vesicles are prepared by modification with a γ3 peptide on the surface (γ3‐RM) for precise targeting. Finally, γ3‐RM camouflages the nanocore CMZ, to form novel erythrocyte membrane‐camouflaged nanoparticle γ3‐RCMZ. The superior performance of novel nanosystem results from its suitable biocompatibility, nontoxicity, specific targeting, and anti‐inflammatory and bactericidal effects. Its anti‐inflammatory mechanism mainly involves inhibiting the Caspase1‐nuclear factor kappa‐B (Caspase1‐NF‐κB) 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‐inflammatory effects in vivo and in vitro. Therefore, the novel nanosystem (γ3‐RCMZ) provides a new nanotherapy strategy for sepsis treatment.