MOF-based nanozyme grafted with cooperative Pt(IV) prodrug for synergistic anticancer therapy.

Ping-Hsuan Wu, Pei-Fen Cheng, Watchareeya Kaveevivitchai, Teng-Hao Chen

Colloids and surfaces. B, Biointerfaces 2023 May

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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 H2O2 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 H2O2 production. Meanwhile, glucose oxidation catalyzed by GOx not only consumes glucose for starvation therapy, but also promotes the intracellular acidity and H2O2 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. Copyright © 2023 Elsevier B.V. All rights reserved.

Citation

Ping-Hsuan Wu, Pei-Fen Cheng, Watchareeya Kaveevivitchai, Teng-Hao Chen. MOF-based nanozyme grafted with cooperative Pt(IV) prodrug for synergistic anticancer therapy. Colloids and surfaces. B, Biointerfaces. 2023 May;225:113264