原子分散的双金属活性位点作为 HO 自供纳米酶用于有效的化学动力学治疗、化疗和饥饿治疗。

Atomically dispersed bimetallic active sites as HO self-supplied nanozyme for effective chemodynamic therapy, chemotherapy and starvation therapy.

机构信息

Key laboratory of the Ministry of Education for Advanced Catalysis Materials, College of Chemistry and Materials Science, College of Life Science, College of Geography and Environmental Sciences, Zhejiang Normal University, Jinhua 321004, China.

Key laboratory of the Ministry of Education for Advanced Catalysis Materials, College of Chemistry and Materials Science, College of Life Science, College of Geography and Environmental Sciences, Zhejiang Normal University, Jinhua 321004, China; Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou 310015, China.

出版信息

Biomater Adv. 2024 Sep;162:213919. doi: 10.1016/j.bioadv.2024.213919. Epub 2024 Jun 2.

Abstract

Tumor microenvironment (TME)-responsive chemodynamic therapy (CDT) is severely hindered by insufficient intracellular HO level that seriously deteriorates antitumor efficacy, albeit with its extensively experimental and theoretical research. Herein, we designed atomically dispersed FeCo dual active sites anchored in porous carbon polyhedra (termed FeCo/PCP), followed by loading with glucose oxidase (GOx) and anticancer doxorubicin (DOX), named FeCo/PCP-GOx-DOX, which converted glucose into toxic hydroxyl radicals. The loaded GOx can either decompose glucose to self-supply HO or provide fewer nutrients to feed the tumor cells. The as-prepared nanozyme exhibited the enhanced in vitro cytotoxicity at high glucose by contrast with those at less or even free of glucose, suggesting sufficient accumulation of HO and continual transformation to OH for CDT. Besides, the FeCo/PCP-GOx-DOX can subtly integrate starvation therapy, the FeCo/PCP-initiated CDT, and DOX-inducible chemotherapy (CT), greatly enhancing the therapeutic efficacy than each monotherapy.

摘要

肿瘤微环境(TME)响应的化学动力学治疗(CDT)受到细胞内 HO 水平不足的严重阻碍,尽管对此进行了广泛的实验和理论研究,但仍严重降低了抗肿瘤疗效。在此,我们设计了锚定在多孔碳多面体中的原子分散的 FeCo 双活性位点(称为 FeCo/PCP),随后负载葡萄糖氧化酶(GOx)和抗癌阿霉素(DOX),命名为 FeCo/PCP-GOx-DOX,它将葡萄糖转化为有毒的羟基自由基。负载的 GOx 可以分解葡萄糖来自我供应 HO,或者提供更少的营养物质来喂养肿瘤细胞。与低葡萄糖或无葡萄糖相比,所制备的纳米酶在高葡萄糖下表现出增强的体外细胞毒性,这表明 HO 的充分积累和持续转化为 OH 以进行 CDT。此外,FeCo/PCP-GOx-DOX 可以巧妙地整合饥饿疗法、FeCo/PCP 引发的 CDT 和 DOX 诱导的化疗(CT),比每种单一疗法都能显著提高治疗效果。

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