Department of Chemical Engineering, Hierarchical Green-Energy Materials (Hi-GEM) Research Center, National Cheng Kung University, Tainan City 70101, Taiwan; School of Pharmacy, National Cheng Kung University, Tainan City 70101, Taiwan.
Department of Chemical Engineering, Hierarchical Green-Energy Materials (Hi-GEM) Research Center, National Cheng Kung University, Tainan City 70101, Taiwan.
Colloids Surf B Biointerfaces. 2023 May;225:113264. doi: 10.1016/j.colsurfb.2023.113264. Epub 2023 Mar 10.
Manipulating Fenton chemistry in tumor microenvironment (TME) for the generation of reactive oxygen species is an effective strategy for chemodynamic therapy. However, this is usually restricted by limited intracellular content of HO and insufficient acidic environment at the tumor site. Herein, a ferric metal-organic framework (MOF) is covalently grafted with a prodrug of cisplatin (Pt(IV) prodrug) and loaded with a biocatalyst glucose oxidase (GOx) to afford a nanozyme MOF-Pt(IV)@GOx for cascade reactions. In this system, the attached Pt(IV) prodrug on MOF plays a significant role in the cooperative enhancement of GOx loading and chemotherapy. The high concentration of glutathione in TME reduces Fe(III) to Fe(II) for Fenton reaction, and converts Pt(IV) prodrug to cisplatin for DNA targeting and HO production. Meanwhile, glucose oxidation catalyzed by GOx not only consumes glucose for starvation therapy, but also promotes the intracellular acidity and HO supply in TME, which are in favor of Fenton reaction. Both in vitro and in vivo studies demonstrate that MOF-Pt(IV)@GOx enables remarkable anticancer efficacy due to the synergistic trimodal therapy consisting of ferroptosis, starvation therapy, and chemotherapy.
在肿瘤微环境(TME)中操纵芬顿化学以产生活性氧是化学动力学治疗的有效策略。然而,这通常受到 HO 的细胞内含量有限和肿瘤部位酸性环境不足的限制。在此,通过共价嫁接顺铂(Pt(IV)前药)的前药和负载生物催化剂葡萄糖氧化酶(GOx),将铁基金属有机骨架(MOF)制成纳米酶 MOF-Pt(IV)@GOx 以进行级联反应。在该体系中,MOF 上附着的 Pt(IV)前药在协同增强 GOx 负载和化学疗法方面发挥了重要作用。TME 中高浓度的谷胱甘肽将 Fe(III)还原为 Fe(II)以进行芬顿反应,并将 Pt(IV)前药转化为顺铂以进行 DNA 靶向和 HO 生成。同时,GOx 催化的葡萄糖氧化不仅消耗葡萄糖进行饥饿治疗,而且还促进 TME 中的细胞内酸度和 HO 供应,有利于芬顿反应。体外和体内研究均表明,由于由铁死亡、饥饿治疗和化学治疗组成的协同三模态治疗,MOF-Pt(IV)@GOx 能够实现显著的抗癌疗效。
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