特异性清除衰老细胞的双药纳米递送系统用于治疗肾衰竭  

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

作　　者：金世奇 李文 黄千笑 曾旋 张先正 Shi-Qi Jin;Wen Li;Qian-Xiao Huang;Xuan Zeng;Xian-Zheng Zhang(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)

机构地区：[1]Key Laboratory of Biomedical Polymers of Ministry of Education&Department of Chemistry,Wuhan University,Wuhan 430072,China [2]Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center,Zhongnan Hospital of Wuhan University,Wuhan 430071,China

出　　处：《Science China Materials》2024年第8期2486-2495,共10页中国科学（材料科学）（英文版）

基　　金：supported by the National Natural Science Foundation of China(52273148,52333004,and 22135005)。

摘　　要：清除衰老细胞是延缓衰老或治疗衰老相关疾病的一种有前途的方法.目前,达沙替尼和槲皮素的组合是研究最为广泛的衰老细胞裂解剂.然而,这两种药物的药代动力学和组织分布不同,迫切需要一种靶向递送策略使其能够同步到达组织或器官.本文设计了一种双药纳米递送系统(L-DQ),以达沙替尼和槲皮素纳米粒子(DQ)为核心,通过将纳米粒子与靶向蛋白相结合,使其具有靶向特定器官的能力.将DQ与溶菌酶结合得到能够靶向肾脏并清除肾脏衰老细胞的L-DQ.L-DQ能够特异性清除衰老细胞而不损害非衰老细胞,有效降低了受损肾脏的衰老细胞比例,促进了肾功能的恢复.这种双药纳米递送系统有助于靶向递送衰老细胞裂解剂至特定器官,为防治衰老相关疾病提供了一种潜在的策略.Clearing senescent cells(SnCs)have emerged as a promising strategy for delaying aging and treating agingrelated 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.

关 键 词：达沙替尼 递送系统 裂解剂 衰老细胞 肾衰竭 药代动力学 肾功能 槲皮素 

分 类 号：R943[医药卫生—药剂学] TB383.1[医药卫生—药学]