Li Shengzhou, Duan Fei, Qiu Zhiwen, Nan Zhuofan, Cao Xiangqian, Yang Chenkai, Li Wei, Shen Bing
Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China.
Department of Nanomedicine, Translational Medicine Research Center, & Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Naval Medical University, Shanghai, 200433, China.
Adv Healthc Mater. 2025 Jun;14(16):e2500696. doi: 10.1002/adhm.202500696. Epub 2025 May 20.
Ischemia-reperfusion injury (IRI) during kidney transplantation is linked to oxidative stress induced by excessive reactive oxygen species (ROS), which causes the injury of transplanted kidney, leading to further intensified organ shortages. Protein-based antioxidants have been developed for ROS scavenging via cascade biocatalyst. The in situ growth of metal nanozymes on proteins effectively decreases the steric hindrance between active sites, improving the efficiency of cascade biocatalysts. However, the poor stability of protein during the process of preparation and intracellular delivery leads to low therapeutic effects. In this study, three different functional polymers are conjugated to SOD for the formation of micelles. Surprisingly, it is found that the conjugated ultra-acid sensitive polymer efficiently preserves the enzymatic activity of SOD, due to great endo/lysosomal escape capacity. Subsequently, SOD micelles (SOE) are used as a template to prepare SOE-Pt (SOEP) through in situ growth of Pt with vicinal enzymatic active sites. The preparation process minimally impacts on the activity of SOD, owing to improved stability. The system exhibits effective cascade ROS scavenging, significantly reducing kidney damage and inflammation caused by IRI. The research offers a novel approach for addressing IRI challenges in organ transplantation and provides a promising strategy to mitigate organ shortages.
肾移植过程中的缺血再灌注损伤（IRI）与过量活性氧（ROS）诱导的氧化应激有关，ROS会导致移植肾损伤，进而加剧器官短缺问题。基于蛋白质的抗氧化剂已被开发用于通过级联生物催化剂清除ROS。金属纳米酶在蛋白质上的原位生长有效降低了活性位点之间的空间位阻，提高了级联生物催化剂的效率。然而，蛋白质在制备和细胞内递送过程中稳定性较差，导致治疗效果不佳。在本研究中，三种不同的功能聚合物与超氧化物歧化酶（SOD）共轭形成胶束。令人惊讶的是，由于具有强大的内吞/溶酶体逃逸能力，发现共轭的超酸敏感聚合物能有效保留SOD的酶活性。随后，以SOD胶束（SOE）为模板，通过具有邻近酶活性位点的Pt的原位生长制备了SOE-Pt（SOEP）。由于稳定性提高，制备过程对SOD活性的影响最小。该系统表现出有效的级联ROS清除能力，显著减少了IRI引起的肾损伤和炎症。该研究为解决器官移植中的IRI挑战提供了一种新方法，并为缓解器官短缺提供了一种有前景的策略。
