A precise dual-drug codelivery nanosystem for treating kidney failure by eliminating senescent cells

Abstract

Clearing senescent cells (SnCs) have emerged as a promising strategy for delaying aging and treating aging-related diseases. The combined administration of dasatinib and quercetin has been widely employed for the elimination of SnCs. However, the therapeutic effectiveness of these two drugs is restricted because they possess distinct pharmacokinetics and biodistributions in vivo. Hence, there is a pressing need to devise a strategy for the targeted synchronous delivery of these two drugs. Here, a dual-drug codelivery nanosystem (lysozyme-dasatinib and quercetin nanoparticles, L-DQ) was developed by integrating DQ through electrostatic interactions. Furthermore, the surfaces of these nanoparticles were modified with lysozyme, enhancing their ability to specifically target the kidney for efficient clearance of SnCs. Through in vivo and in vitro experiments, the effective elimination of SnCs from the kidney and accelerated recovery of renal function by L-DQ were demonstrated. This study provides a potential strategy for the treatment of multiple aging-related diseases by the targeted delivery of senolytics to specific organs.