College of Polymer Science and Engineering, Med-X Center for Materials, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China.
West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
Small. 2023 May;19(18):e2206911. doi: 10.1002/smll.202206911. Epub 2023 Feb 10.
The external-stimulation-induced reactive-oxygen-species (ROS) generation has attracted increasing attention in therapeutics for malignant tumors. However, engineering a nanoplatform that integrates with efficient biocatalytic ROS generation, ultrasound-amplified ROS production, and simultaneous relief of tumor hypoxia is still a great challenge. Here, we create new semiconducting titanate-supported Ru clusterzymes (RuNC/BTO) for ultrasound-amplified biocatalytic tumor nanotherapies. The morphology and chemical/electronic structure analysis prove that the biocatalyst consists of Ru nanoclusters that are tightly stabilized by Ru-O coordination on BaTiO . The peroxidase (POD)- and halogenperoxidase-like biocatalysis reveals that the RuNC/BTO can produce abundant •O radicals. Notably, the RuNC/BTO exhibits the highest turnover number (63.29 × 10 s ) among the state-of-the-art POD-mimics. Moreover, the catalase-like activity of the RuNC/BTO facilitates the decomposition of H O to produce O for relieving the hypoxia of the tumor and amplifying the ROS level via ultrasound irradiation. Finally, the systematic cellular and animal experiments have validated that the multi-modal strategy presents superior tumor cell-killing effects and suppression abilities. We believe that this work will offer an effective clusterzyme that can adapt to the tumor microenvironment-specific catalytic therapy and also provide a new pathway for engineering high-performance ROS production materials across broad therapeutics and biomedical fields.
外源性刺激诱导的活性氧（ROS）生成在恶性肿瘤治疗中受到越来越多的关注。然而，工程学上设计一种整合高效生物催化 ROS 生成、超声放大 ROS 产生以及同时缓解肿瘤缺氧的纳米平台仍然是一个巨大的挑战。在这里，我们创建了新型半导体钛酸盐负载的钌团簇酶（RuNC/BTO），用于超声放大的生物催化肿瘤纳米治疗。形态和化学/电子结构分析证明，生物催化剂由紧密稳定的 Ru 纳米簇组成，这些纳米簇通过 BaTiO 上的 Ru-O 配位稳定。过氧化物酶（POD）和卤过氧化物酶样生物催化表明，RuNC/BTO 可以产生丰富的•O 自由基。值得注意的是，RuNC/BTO 表现出最高的周转数（63.29×10 s ），超过了目前最先进的 POD 模拟物。此外，RuNC/BTO 的过氧化氢酶样活性有助于 H 2 O 2 的分解，产生 O 2 ，以缓解肿瘤缺氧，并通过超声辐射放大 ROS 水平。最后，系统的细胞和动物实验验证了多模态策略具有优越的肿瘤细胞杀伤效果和抑制能力。我们相信，这项工作将提供一种有效的团簇酶，能够适应肿瘤微环境特异性催化治疗，并为工程高性能 ROS 产生材料提供新途径，应用于广泛的治疗学和生物医学领域。
