Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China.
Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China.
J Nanobiotechnology. 2021 Oct 16;19(1):325. doi: 10.1186/s12951-021-01074-1.
Chemodynamic therapy (CDT) catalyzed by transition metal and starvation therapy catalyzed by intracellular metabolite oxidases are both classic tumor treatments based on nanocatalysts. CDT monotherapy has limitations including low catalytic efficiency of metal ions and insufficient endogenous hydrogen peroxide (HO). Also, single starvation therapy shows limited ability on resisting tumors. The "metal-oxidase" cascade catalytic system is to introduce intracellular metabolite oxidases into the metal-based nanoplatform, which perfectly solves the shortcomings of the above-mentioned monotherapiesIn this system, oxidases can not only consume tumor nutrients to produce a "starvation effect", but also provide CDT with sufficient HO and a suitable acidic environment, which further promote synergy between CDT and starvation therapy, leading to enhanced antitumor effects. More importantly, the "metal-oxidase" system can be combined with other antitumor therapies (such as photothermal therapy, hypoxia-activated drug therapy, chemotherapy, and immunotherapy) to maximize their antitumor effects. In addition, both metal-based nanoparticles and oxidases can activate tumor immunity through multiple pathways, so the combination of the "metal-oxidase" system with immunotherapy has a powerful synergistic effect. This article firstly introduced the metals which induce CDT and the oxidases which induce starvation therapy and then described the "metal-oxidase" cascade catalytic system in detail. Moreover, we highlight the application of the "metal-oxidase" system in combination with numerous antitumor therapies, especially in combination with immunotherapy, expecting to provide new ideas for tumor treatment.
化学动力学治疗（CDT）由过渡金属催化，以及细胞内代谢物氧化酶催化的饥饿治疗，都是基于纳米催化剂的经典肿瘤治疗方法。CDT 单一疗法存在一些局限性，包括金属离子的催化效率低和内源性过氧化氢（HO）不足。此外，单一饥饿治疗在抵抗肿瘤方面的能力有限。“金属-氧化酶”级联催化系统是将细胞内代谢物氧化酶引入基于金属的纳米平台中，这完美地解决了上述单一疗法的缺点。在该系统中，氧化酶不仅可以消耗肿瘤营养物质产生“饥饿效应”，还可以为 CDT 提供充足的 HO 和合适的酸性环境，从而进一步促进 CDT 和饥饿治疗之间的协同作用，增强抗肿瘤效果。更重要的是，“金属-氧化酶”系统可以与其他抗肿瘤疗法（如光热疗法、缺氧激活药物治疗、化学疗法和免疫疗法）相结合，以最大限度地发挥其抗肿瘤效果。此外，金属纳米粒子和氧化酶都可以通过多种途径激活肿瘤免疫，因此“金属-氧化酶”系统与免疫疗法的结合具有强大的协同作用。本文首先介绍了诱导 CDT 的金属和诱导饥饿治疗的氧化酶，然后详细描述了“金属-氧化酶”级联催化系统。此外，我们强调了“金属-氧化酶”系统在与多种抗肿瘤疗法相结合，特别是与免疫疗法相结合的应用，期望为肿瘤治疗提供新的思路。
