Manganese Carbonyl-Loaded Hollow Mesoporous Silica Nanoparticles Coated with Neutrophil Membranes for Acute Kidney Injury Therapy

Abstract

Acute kidney injury (AKI) has a very high incidence in hospitalized patients, but it lacks effective therapy clinically. Its pathogenesis is associated with capillary hypoperfusion around renal tubules, production of reactive oxygen free radicals (ROS), and infiltration of inflammatory cells. Endogenous carbon monoxide (CO) can protect cells or organs by vasodilation, anti-inflammation, and reducing oxidative stress injury. However, direct exogenous CO supplementation is difficult to control the exact dose, and excessive CO has obvious toxicity, which is difficult to be applied in clinical treatment. In this study, we constructed H2O2-responsive nanomedicine for CO therapy of AKI by loading manganese carbonyl (MnCO) onto the hollow mesoporous silicon nanoparticles (hMSN), which were coated with a neutrophil membrane with the insertion of phosphatidylserine (PS) into the membrane surface (MnCO@hMSN@NM-PS). MnCO@hMSN@NM-PS was located in the renal tubules of AKI through the biomimetic chemotaxis of the neutrophil membrane to the inflammation site and the active binding of PS to kidney injury molecule-1 (KIM-1), which was overexpressed in damaged renal tubular epithelial cells. MnCO@hMSN@NM-PS had a good protective effect on oxidative damage of renal tubular cells in vitro and glycerol-induced AKI in vivo. MnCO@hMSN@NM-PS offers hope for the treatment of AKI.