Department of Health Toxicology, Faculty of Naval Medicine, Naval Medical University, Shanghai, 200433, China.
Operating Theatre, Department of Anaesthesiology, First Affliated Hospital of Naval Medical University, Shanghai, 200433, China.
J Mater Chem B. 2024 Jan 17;12(3):710-719. doi: 10.1039/d3tb02018e.
The main challenges of nanozyme-based tumor catalytic therapy (NCT) lie in the unsatisfactory catalytic activity accompanied by a complex tumor microenvironment (TME). A few nanozymes have been designed to possess both enzyme-like catalytic activities and photothermal properties; however, the previously reported nanozymes mainly utilize the inefficient and unsafe NIR-I laser, which has a low maximum permissible exposure limit and a limited penetration depth. Herein, we report for the first time an all-in-one strategy to realize mild NIR-II photothermally amplified NCT by synthesizing amorphous CoSnO nanocubes with efficient triple enzyme-like catalytic activities and photothermal conversion properties. The presence of Co and Sn endows CoSnO nanocubes with the triple enzyme-like catalytic activities, not only achieving enhanced reactive oxygen species (ROS) generation through the Co-mediated peroxidase-like catalytic reaction to generate ˙OH and Sn-mediated depletion of overexpressed GSH, but also realizing the catalytic decomposition of endogenous HO for relieving tumor hypoxia. More importantly, the obtained CoSnO nanocubes with a high photothermal conversion efficiency of 82.1% at 1064 nm could achieve mild hyperthermia (43 °C), which further improves the triple enzyme-like catalytic activities of the CoSnO nanozyme. The synergetic therapeutic efficacy of the NIR-II-responsive CoSnO nanozyme through mild NIR-II PTT-enhanced NCT could realize all-in-one multimodal tumor therapy to completely eliminate tumors without recurrence. This study will open a new avenue to explore NIR-II-photoresponsive nanozymes for efficient tumor therapy.
基于纳米酶的肿瘤催化治疗（NCT）的主要挑战在于催化活性不理想，同时伴有复杂的肿瘤微环境（TME）。已经设计了一些纳米酶来同时具有酶样催化活性和光热特性；然而，以前报道的纳米酶主要利用低效和不安全的近红外 I 激光，其最大允许暴露限值低，穿透深度有限。在此，我们首次报道了一种通过合成具有高效三酶样催化活性和光热转换特性的非晶态 CoSnO 纳米立方体来实现温和的近红外 II 光热放大 NCT 的一体化策略。Co 和 Sn 的存在赋予了 CoSnO 纳米立方体三酶样催化活性，不仅通过 Co 介导的过氧化物酶样催化反应产生˙OH 和 Sn 介导的过表达 GSH 耗竭来增强活性氧（ROS）的产生，而且实现了内源性 HO 的催化分解以缓解肿瘤缺氧。更重要的是，获得的 CoSnO 纳米立方体在 1064nm 处具有 82.1%的高光热转换效率，可实现温和的热疗（43°C），这进一步提高了 CoSnO 纳米酶的三酶样催化活性。通过温和的近红外 II PTT 增强 NCT 的近红外 II 响应 CoSnO 纳米酶的协同治疗效果，可以实现一体化多模态肿瘤治疗，完全消除肿瘤而不复发。这项研究将为探索用于高效肿瘤治疗的近红外 II 光响应纳米酶开辟新途径。
