Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Key Laboratory of Polymer Materials, College of Health Science and Engineering, School of Materials Science and Engineering, Hubei University, Wuhan 430062, China.
Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Key Laboratory of Polymer Materials, College of Health Science and Engineering, School of Materials Science and Engineering, Hubei University, Wuhan 430062, China.
J Colloid Interface Sci. 2024 Jul 15;666:244-258. doi: 10.1016/j.jcis.2024.04.036. Epub 2024 Apr 6.
Starvation therapy has shown promise as a cancer treatment, but its efficacy is often limited when used alone. In this work, a multifunctional nanoscale cascade enzyme system, named CaCO@MnO-NH@GOx@PVP (CMGP), was fabricated for enhanced starvation/chemodynamic combination cancer therapy. CMGP is composed of CaCO nanoparticles wrapped in a MnO shell, with glucose oxidase (GOx) adsorbed and modified with polyvinylpyrrolidone (PVP). MnO decomposes HO in cancer cells into O, which enhances the efficiency of GOx-mediated starvation therapy. CaCO can be decomposed in the acidic cancer cell environment, causing Ca overload in cancer cells and inhibiting mitochondrial metabolism. This synergizes with GOx to achieve more efficient starvation therapy. Additionally, the HO and gluconic acid produced during glucose consumption by GOx are utilized by MnO with catalase-like activity to enhance O production and Mn release. This process accelerates glucose consumption, reactive oxygen species (ROS) generation, and CaCO decomposition, promoting the Ca release. CMGP can alleviate tumor hypoxia by cycling the enzymatic cascade reaction, which increases enzyme activity and combines with Ca overload to achieve enhanced combined starvation/chemodynamic therapy. In vitro and in vivo studies demonstrate that CMGP has effective anticancer abilities and good biosafety. It represents a new strategy with great potential for combined cancer therapy.
饥饿疗法已显示出作为癌症治疗的潜力，但单独使用时其疗效往往有限。在这项工作中，制备了一种多功能纳米级级联酶系统，命名为 CaCO@MnO-NH@GOx@PVP（CMGP），用于增强饥饿/化学动力学联合癌症治疗。CMGP 由 CaCO 纳米颗粒包裹在 MnO 壳中，吸附并修饰有葡萄糖氧化酶（GOx）和聚乙烯吡咯烷酮（PVP）。MnO 在癌细胞中分解 HO 成 O，从而提高了 GOx 介导的饥饿治疗效率。CaCO 可以在酸性的癌细胞环境中分解，导致癌细胞中的 Ca 超载并抑制线粒体代谢。这与 GOx 协同作用，实现更有效的饥饿治疗。此外，GOx 消耗葡萄糖产生的 HO 和葡萄糖酸被具有类过氧化物酶活性的 MnO 利用，以增强 O 生成和 Mn 释放。这一过程加速了葡萄糖消耗、活性氧（ROS）生成和 CaCO 分解，促进了 Ca 的释放。CMGP 通过循环酶级联反应缓解肿瘤缺氧，从而提高酶活性并与 Ca 超载结合，实现增强的联合饥饿/化学动力学治疗。体外和体内研究表明，CMGP 具有有效的抗癌能力和良好的生物安全性。它代表了一种具有巨大潜力的联合癌症治疗的新策略。
