Liu Hengke, Lei Shan, Li Hongyu, Wu Jiayingzi, He Ting, Lin Jing, Huang Peng
Marshall Laboratory of Biomedical Engineering, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Laboratory of Evolutionary Theranostics (LET), International Cancer Center, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, People's Republic of China.
Nanomicro Lett. 2025 May 12;17(1):253. doi: 10.1007/s40820-025-01735-y.
Single-atom nanozymes (SAzymes) hold significant potential for tumor catalytic therapy, but their effectiveness is often compromised by low catalytic efficiency within tumor microenvironment. This efficiency is mainly influenced by key factors including hydrogen peroxide (HO) availability, acidity, and temperature. Simultaneous optimization of these key factors presents a significant challenge for tumor catalytic therapy. In this study, we developed a comprehensive strategy to refine single-atom catalytic kinetics for enhancing tumor catalytic therapy through dual-enzyme-driven cascade reactions. Iridium (Ir) SAzymes with high catalytic activity and natural enzyme glucose oxidase (GOx) were utilized to construct the cascade reaction system. GOx was loaded by Ir SAzymes due to its large surface area. Then, the dual-enzyme-driven cascade reaction system was modified by cancer cell membranes for improving biocompatibility and achieving tumor homologous targeting ability. GOx catalysis reaction could produce abundant HO and lower the local pH, thereby optimizing key reaction-limiting factors. Additionally, upon laser irradiation, Ir SAzymes could raise local temperature, further enhancing the catalytic efficiency of dual-enzyme system. This comprehensive optimization maximized the performance of Ir SAzymes, significantly improving the efficiency of catalytic therapy. Our findings present a strategy of refining single-atom catalytic kinetics for tumor homologous-targeted catalytic therapy.
单原子纳米酶在肿瘤催化治疗方面具有巨大潜力，但其有效性常常因肿瘤微环境中催化效率低而受到影响。这种效率主要受包括过氧化氢（H₂O₂）可用性、酸度和温度等关键因素的影响。同时优化这些关键因素对肿瘤催化治疗提出了重大挑战。在本研究中，我们开发了一种综合策略来优化单原子催化动力学，通过双酶驱动的级联反应增强肿瘤催化治疗。利用具有高催化活性的铱（Ir）单原子纳米酶和天然酶葡萄糖氧化酶（GOx）构建级联反应体系。由于Ir单原子纳米酶的大表面积，GOx被负载在其上。然后，用癌细胞膜修饰双酶驱动的级联反应体系，以提高生物相容性并实现肿瘤同源靶向能力。GOx催化反应可产生大量H₂O₂并降低局部pH值，从而优化关键反应限制因素。此外，在激光照射下，Ir单原子纳米酶可提高局部温度，进一步增强双酶体系的催化效率。这种综合优化使Ir单原子纳米酶的性能最大化，显著提高了催化治疗的效率。我们的研究结果提出了一种优化单原子催化动力学用于肿瘤同源靶向催化治疗的策略。
