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沸石咪唑骨架衍生的富含 Zn-CoO/N-掺杂多孔碳具有多种类酶活性,用于协同癌症治疗。

Zeolitic imidazole framework-derived rich-Zn-CoO/N-doped porous carbon with multiple enzyme-like activities for synergistic cancer 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.

Central Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, China.

出版信息

J Colloid Interface Sci. 2024 Jul;665:1065-1078. doi: 10.1016/j.jcis.2024.03.186. Epub 2024 Mar 29.

Abstract

Reactive oxygen species (ROS)-centered chemodynamic therapy (CDT) holds significant potential for tumor-specific treatment. However, insufficient endogenous HO and extra glutathione within tumor microenvironment (TME) severely deteriorate the CDT's effectiveness. Herein, rich-Zn-CoO/N-doped porous carbon (Zn-CoO/NC) was fabricated by two-step pyrolysis, and applied to build high-efficiency nano-platform for synergistic cancer therapy upon combination with glucose oxidase (GOx), labeled Zn-CoO/NC-GOx for clarity. Specifically, the multiple enzyme-like activities of the Zn-CoO/NC were scrutinously investigated, including peroxidase-like activity to convert HO to O, catalase-like activity to decompose HO into O, and oxidase-like activity to transform O to O, which achieved the CDT through the catalytic cascade reaction. Simultaneously, GOx reacted with intracellular glucose to produce gluconic acid and HO, realizing starvation therapy. In the acidic TME, the Zn-CoO/NC-GOx rapidly caused intracellular Zn pool overload and disrupted cellular homeostasis for ion-intervention therapy. Additionally, the Zn-CoO/NC exhibited glutathione peroxidase-like activity, which consumed glutathione in tumor cells and reduced the ROS consumption for ferroptosis. The tumor treatments offer some constructive insights into the nanozyme-mediated catalytic medicine, coupled by avoiding the TME limitations.

摘要

活性氧(ROS)为中心的化学动力学治疗(CDT)在肿瘤特异性治疗方面具有重要潜力。然而,肿瘤微环境(TME)中内源性 HO 和额外的谷胱甘肽含量不足,严重降低了 CDT 的效果。在此,通过两步热解制备了富含 Zn-CoO/N 掺杂多孔碳(Zn-CoO/NC),并通过与葡萄糖氧化酶(GOx)结合,应用于构建高效协同癌症治疗纳米平台,明确标记为 Zn-CoO/NC-GOx。具体而言,详细研究了 Zn-CoO/NC 的多种酶样活性,包括过氧化物酶样活性将 HO 转化为 O,过氧化氢酶样活性将 HO 分解为 O,以及氧化酶样活性将 O 转化为 O,从而通过催化级联反应实现 CDT。同时,GOx 与细胞内的葡萄糖反应生成葡萄糖酸和 HO,实现饥饿治疗。在酸性 TME 中,Zn-CoO/NC-GOx 迅速引起细胞内锌池过载,并破坏细胞内离子平衡以实现离子干预治疗。此外,Zn-CoO/NC 还表现出谷胱甘肽过氧化物酶样活性,消耗肿瘤细胞中的谷胱甘肽,减少用于铁死亡的 ROS 消耗。该肿瘤治疗为纳米酶介导的催化医学提供了一些建设性的见解,同时避免了 TME 的限制。

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