Deng Hanzhi, Qu Ying, Chu Bingyang, Luo Tianying, Pan Meng, Yuan Liping, Mo Dong, Bei Zhongwu, Yang Tingyu, Li Xicheng, Lu Yi, Qian Zhiyong
Department of Biotherapy and Department of Hematology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
Department of Biotherapy and Department of Hematology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
Biomaterials. 2025 Jun;317:123072. doi: 10.1016/j.biomaterials.2024.123072. Epub 2024 Dec 30.
Acute kidney injury (AKI) is a common clinical syndrome characterized by the rapid loss of renal filtration function. No standard therapeutic agent option is currently available. The development and progression of AKI is a continuous and dynamical pathological process. Oxidative stress and inflammatory responses are the primary influencing factors. Here, we developed a biomimetic nano-system (MM-PtNCs) with reactive oxygen species (ROS)-responsive platinum nanozyme clusters (PtNCs) wrapped in macrophage membrane (MM) to alleviate AKI by modulating oxidative stress and inflammation. The inflammatory cytokines receptors retained on MM surface allowed the biomimetic nano-system to target renal inflammation and neutralize these pro-inflammatory cytokines to ameliorate inflammation. PtNCs exhibit free radical scavenging-ability and catalase (CAT)-like activity to scavenge ROS and regulate the oxidative stress situations both in injured cells and tissues. Meanwhile, it could responsively dissociate into ultrasmall platinum nanoparticles under AKI-specific ROS conditions to eliminate ROS and eventually excreted through the renal filtration system. In a mouse model of ischemia/reperfusion-induced AKI, systemic injection of MM-PtNCs significantly reduced renal damage and restored kidney function. Additionally, MM-PtNCs effectively prevented the progression of AKI to chronic kidney disease. In conclusion, MM-PtNCs may propose a multi-faceted regulatory approach for clinical AKI treatment.
急性肾损伤（AKI）是一种常见的临床综合征，其特征为肾脏滤过功能迅速丧失。目前尚无标准的治疗药物选择。AKI的发生和发展是一个持续且动态的病理过程。氧化应激和炎症反应是主要影响因素。在此，我们构建了一种仿生纳米系统（MM-PtNCs），其具有包裹在巨噬细胞膜（MM）中的活性氧（ROS）响应性铂纳米酶簇（PtNCs），通过调节氧化应激和炎症来缓解AKI。保留在MM表面的炎性细胞因子受体使该仿生纳米系统能够靶向肾脏炎症并中和这些促炎细胞因子以减轻炎症。PtNCs具有自由基清除能力和过氧化氢酶（CAT）样活性，可清除ROS并调节受损细胞和组织中的氧化应激状况。同时，它能在AKI特异性ROS条件下响应性地解离为超小铂纳米颗粒以清除ROS，并最终通过肾脏滤过系统排出。在缺血/再灌注诱导的AKI小鼠模型中，全身注射MM-PtNCs可显著减轻肾脏损伤并恢复肾功能。此外，MM-PtNCs有效预防了AKI向慢性肾脏病的进展。总之，MM-PtNCs可能为临床AKI治疗提供一种多方面的调节方法。
