#6508 THE EFFECTS AND MECHANISM OF BRAIN-TARGETING DRUG-LOADED EXOSOMES ON ADRIAMYCIN NEPHROPATHY MODEL

Abstract

Abstract Background and Aims Chronic kidney disease (CKD) is a common clinical syndrome, and the current clinical efficacy is still limited. Our previous study confirmed that a small amount of losartan injected into the central lateral ventricle can effectively protect the kidneys, but the route of administration limits its clinical application. As a drug carrier, exosomes have several advantages and are expected to support drug delivery. Therefore, this study aims to develop a brain-targeting exosome complex to provide a new idea for the treatment of CKD. Method In this study, the brain-targeting exosome complex (ExoACP) was synthesized by co-cultivation. The markers of ExoACP were detected by immunoblotting. The structure and particle size distribution were observed by TEM and NTA. Angiotensin II receptor antagonist losartan (ExoACP@Los) was loaded on ExoACP by electroporation. The mice of Adriamycin (ADR)-induced nephropathy were divided into 5 groups: Control, ADR, ADR + Los (IG), ADR + ExoACP (iv.), ADR + ExoACP@Los (iv.). Corresponding treatment was given every other day from the 3rd week after modeling, and all mice were sacrificed at the 5th week, serum and renal tissue was collected for the following experiments. Results This study found that the exosome markers of ExoACP were highly expressed. The Exo and Ang-CP05-Exo were disc-like structures, and the size of the latter was larger than that of the former, suggesting that ExoACP was successfully modified on the surface of Exo. The modification efficiency of ExoACP on Exo was as high as 96.1%. Compared with free Exo, the distribution of ExoACP in brain was increased. Blood biochemical results showed that ExoACP and ExoACP@Los had no apparent side-effects on mice (Figure 1). In-vivo, ExoACP@Los treatment significantly improved the levels of kidney function in mice with ADR nephropathy. ExoACP@Los could significantly reduce renal tubular damage, interstitial fibrosis area and degree of glomerular sclerosis, suggesting that ExoACP@Los could improve the injury of renal tissue (Figure 2). Conclusion This study synthesized a drug-loaded exosome complex with brain targeting and good biocompatibility, and significantly improved renal function, renal tissue damage and collagen fiber deposition in the ADR model.