A precise dual-drug codelivery nanosystem for treating kidney failure by eliminating senescent cells
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 pharmacoki-netics 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 interac-tions.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.
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry,Wuhan University,Wuhan 430072,China
Key Laboratory of Biomedical Polymers of Ministry of Education&Department of Chemistry,Wuhan University,Wuhan 430072,China
Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center,Zhongnan Hospital of Wuhan University,Wuhan 430071,China
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