Li Rui, Zhao Weiheng, Wu Tingting, Wang Aifeng, Li Qing, Liu Ying, Xiong Huihua
Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Department of Pharmacy, Henan Provincial People's Hospital, Department of Pharmacy of Centeral China Fuwai Hospital, Centeral China Fuwai Hospital of Zhengzhou University, Zheng Zhou, China.
Front Bioeng Biotechnol. 2022 Oct 24;10:1042646. doi: 10.3389/fbioe.2022.1042646. eCollection 2022.
Radiotherapy (RT) plays a pivotal role in the comprehensive treatment of multiple malignant tumors, exerting its anti-tumor effects through direct induction of double-strand breaks (DSBs) or indirect induction of reactive oxygen species (ROS) production. However, RT resistance remains a therapeutic obstacle that leads to cancer recurrence and treatment failure. In this study, we synthesised a tantalum-carbon-integrated nanozyme with excellent catalase-like (CAT-like) activity and radiosensitivity by immobilising an ultrasmall tantalum nanozyme into a metal-organic framework (MOF)-derived carbon nanozyme through reduction. The integrated tantalum nanozyme significantly increased the CAT activity of the carbon nanozyme, which promoted the production of more oxygen and increased the ROS levels. By improving hypoxia and increasing the level of ROS, more DNA DSBs occur at the cellular level, which, in turn, improves the sensitivity of RT. Moreover, tantalum-carbon-integrated nanozymes combined with RT have demonstrated notable anti-tumor activity . Therefore, exploiting the enzymatic activity and the effect of ROS amplification of this nanozyme has the potential to overcome resistance to RT, which may offer new horizons for nanozyme-based remedies for biomedical applications.
放射治疗(RT)在多种恶性肿瘤的综合治疗中起着关键作用,通过直接诱导双链断裂(DSB)或间接诱导活性氧(ROS)生成来发挥其抗肿瘤作用。然而,放疗抵抗仍然是一个治疗障碍,会导致癌症复发和治疗失败。在本研究中,我们通过还原法将超小钽纳米酶固定在金属有机框架(MOF)衍生的碳纳米酶中,合成了一种具有优异过氧化氢酶样(CAT样)活性和放射敏感性的钽 - 碳集成纳米酶。集成的钽纳米酶显著提高了碳纳米酶的CAT活性,促进了更多氧气的产生并提高了ROS水平。通过改善缺氧状况和提高ROS水平,在细胞水平上会发生更多的DNA双链断裂,进而提高放疗的敏感性。此外,钽 - 碳集成纳米酶与放疗联合使用已显示出显著的抗肿瘤活性。因此,利用这种纳米酶的酶活性和ROS放大效应有可能克服放疗抵抗,这可能为基于纳米酶的生物医学应用疗法提供新的前景。