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

IF 6.8 2区材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY

Science China Materials Pub Date : 2024-07-17 DOI:10.1007/s40843-024-2864-5

Shi-Qi Jin (, ), Wen Li (, ), Qian-Xiao Huang (, ), Xuan Zeng (, ), Xian-Zheng Zhang (, )

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引用次数: 0

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.

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通过消除衰老细胞治疗肾衰竭的精确双药编码给药纳米系统

清除衰老细胞（SnCs）已成为延缓衰老和治疗衰老相关疾病的一种有前途的策略。达沙替尼和槲皮素的联合用药已被广泛用于清除衰老细胞。然而，由于这两种药物在体内具有不同的药代动力学和生物分布，其治疗效果受到限制。因此，亟需设计出这两种药物的靶向同步给药策略。在此，我们通过静电相互作用将 DQ 整合在一起，开发了一种双药协同给药纳米系统（溶菌酶-达沙替尼和槲皮素纳米颗粒，L-DQ）。此外，还用溶菌酶修饰了这些纳米颗粒的表面，增强了它们特异性靶向肾脏的能力，从而有效清除SnCs。通过体内和体外实验，证明了 L-DQ 能有效清除肾脏中的氯化锡，并加速肾功能的恢复。这项研究为通过向特定器官靶向输送解老剂来治疗多种衰老相关疾病提供了一种潜在的策略。

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来源期刊

Science China Materials Materials Science-General Materials Science

CiteScore

11.40

自引率

7.40%

发文量

949

期刊介绍： Science China Materials (SCM) is a globally peer-reviewed journal that covers all facets of materials science. It is supervised by the Chinese Academy of Sciences and co-sponsored by the Chinese Academy of Sciences and the National Natural Science Foundation of China. The journal is jointly published monthly in both printed and electronic forms by Science China Press and Springer. The aim of SCM is to encourage communication of high-quality, innovative research results at the cutting-edge interface of materials science with chemistry, physics, biology, and engineering. It focuses on breakthroughs from around the world and aims to become a world-leading academic journal for materials science.