An erythrocyte membrane-derived nanosystem for efficient reversal of endothelial injury in sepsis

Abstract Background: Sepsis is caused by a disordered host immune in response to infection and endothelial cells (ECs) perform a crucial role in boosting immunity reaction in the pathophysiology of sepsis and organ failure. The aim of this study is to construct a novel erythrocyte membrane-derived nanosystems to reverse endothelial damage in sepsis. Results: Herein, we generated a nanometer calcium organometallic framework (Ca-MOF) by using chelidonic acid as a ligand and calcium chloride as an ion donor for anti-inflammation. Then, zoliflodacin was loaded into Ca-MOF (CMZ) to sterilize, and nanoscale erythrocyte membrane vesicles were prepared by modification with a γ3 peptide on the surface (γ3-RM) for precise targeting. Finally, the novel erythrocyte membrane-camouflaged nanoparticle γ3-RCMZ was synthesized. The superior performance of novel nanosystem results from its suitable biocompatibility, nontoxicity, specific targeting, and anti-inflammatory and bactericidal effects. Its mechanism mainly involves the Caspase1-NFκB pathway and oxidative stress reduction to alleviate endothelial damage. Moreover, our findings revealed for the first time that the bactericidal drug zoliflodacin also had anti-inflammatory effects in vivo and in vitro. Conclusions: Basing on the suitable biocompatibility, nontoxicity, specific targeting, and anti-inflammatory and bactericidal effects, the novel nanosystem (γ3-RCMZ) provides a new nanotherapy strategy for sepsis treatment. Keywords: Metal-organic frame; Nanodrug delivery system; Sepsis; Endothelial injury; Erythrocyte membrane