The Renal Protective Effects Of Neutrophil Membrane Coated MnCO@hMSN Nanomedicine On The Treatment Of Acute Kidney Injury

The incidence of acute kidney injury(AKI)in hospitalized patients is very high,but it is lack of effective therapy in clinical.Many patients with AKI may progress quickly to chronic kidney disease and worsen the prognosis of the patients significantly.It has been bringing the heavy burden to patients,families and society.The pathogenesis of AKI is related to capillary hypoperfusion around renal tubules,production of reactive oxygen free radicals(ROS)and infiltration of inflammatory cells.Therefore,reducing the contraction of small vessels in the kidney,inhibiting the activity of local ROS and inflammatory response may be an effective mothed to prevent AKI and improve the prognosis of the patients with AKI.The studies had found that endogenous carbon monoxide(CO)can protect cells or organs by vasodilation,anti-inflammation,reducing oxidative stress injury.However,direct exogenous CO supplementation is difficult to control the exact dose of CO.The excessive CO has obvious toxicity,and it is difficult to be applied in clinical treatment.Under certain conditions,the organic metal complex carbon monoxide releasing molecules(CORM)formed by the combination of transition metals and carbonyl groups can produce nontoxic and harmless trace CO,which may play the role of endogenous CO gas signaling molecules.This study selected H2O2-responsive carbonyl manganese(MnCO)as CORM,and synthesize CO controlled-release nanoparticles(MnCO@hMSN)by loading MnCO onto the hollow mesoporous silicon nanoparticles(hMSN),then encapsulate neutrophil membrane(NM)on the surface of the MnCO@hMSN to avoid immune phagocytosis.Then,MnCO@hMSN@NM-PS drug-loaded nanomedicine was prepared by connecting phosphatidylserine(PS)with surface modification of cell membrane for the therapy of AKI.Since injured renal tubular epithelial cells can express high abundance of kidney injury molecule-1(KIM-1 is a receptor of PS)and the biomimetic chemotaxis property of the neutrophil membrane vesicles to the inflammation site,so the administration of MnCO@hMSN@NM-PS nanoparticles via intravenous injection can accurately targeted and concentrated in the local areas of injured renal tubular epithelial cells.The local ROS products in the kidney then act on the carbonyl group of the MnCO@hMSN@NM-PS nanoparticles to release CO.The low concentration of CO could relax the microvessels and improve the local microcirculation.At the same time,the excess ROS in the local of injured kidney were consumed by redox reaction,and reduced the inflammatory reaction of the tubulointerstitial.Our results showed that the MnCO@hMSN@NM-PS has been prepared successful,and it had good protective effects on the oxidative damage of renal tubular cells in vitro and the therapy effects on the AKI induced by glycerol in vivo.MnCO@hMSN@NM-PS offers the hope for the treatment of AKI in clinical.