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A Mn-porphyrinic metal–organic framework immobilizing glucose oxidase for combined photodynamic/chemodynamic/starvation therapy

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Abstract

The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) in tumor treatment has attracted considerable attention. However, tumor hypoxia and glutathione (GSH) overproduction in the tumor tissue restricted the progress of their applications. Herein, a Mn-porphyrinic metal–organic framework (Mn-TCPP) was constructed by the one-pot method and further used for immobilizing glucose oxidase (GOx) to obtain GOx@Mn-TCPP. GOx would rapidly exhaust endogenous glucose into hydrogen peroxide (H2O2) and gluconic acid, thus shutting off the energy supply of tumor cells for starvation treatment. Mn-TCPP catalyzed H2O2 to produce oxygen, regulating the hypoxic tumor microenvironment and in turn improving 1O2 generation under laser irradiation. Interestingly, Mn-TCPP can reduce reactive oxygen species consumption owing to the redox reaction between Mn3+ and GSH, thus greatly enhancing PDT. Furthermore, benefiting from GOx-mediated starvation therapy, Mn2+ produced by Mn3+ reduction can react with sufficient intracellular H2O2 to generate ·OH with high cytotoxicity through a Fenton-like reaction. After treatment by GOx@Mn-TCPP under laser irradiation in vitro, the cell viability of 4T1 and A549 tumor cells reached to 20%, reflecting GOx@Mn-TCPP could give full play to the advantages of PDT/CDT/starvation therapy. The results in vivo demonstrated that GOx@Mn-TCPP mediated synergistic cascade therapy could significantly inhibit tumor growth and improve the therapeutic effect.

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The data generated during and/or analyszed in this article are available from the corresponding author on the reasonable request.

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Acknowledgements

This work was supported by the Natural Science Foundation of Shandong Province (Nos. ZR2023MB139, ZR2023QB057), and the Key R&D Projects of Linyi City (2022022).

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**n-Ran Sun and Hao-Ming Yuan wrote the draft; **n-Ran Sun and Guo-Da Zhang collected the data; Chao Wang and Hao-Ming Yuan revised the paper, Shu-Juan Sun and Peng-Fei Shi contributed to conceived the idea of the study. All authors contributed to the writing and revisions. **n-Ran Sun and Hao-Ming Yuan contributed equally to this work and can be considered co-first authors.

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Correspondence to Shu-Juan Sun or Peng-Fei Shi.

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Sun, XR., Yuan, HM., Zhang, GD. et al. A Mn-porphyrinic metal–organic framework immobilizing glucose oxidase for combined photodynamic/chemodynamic/starvation therapy. Tungsten (2024). https://doi.org/10.1007/s42864-024-00283-z

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