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Modulation of tumor microenvironment by metal-organic-framework-derived nanoenzyme for enhancing nucleus-targeted photodynamic therapy

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Abstract

Photodynamic therapy (PDT) is a promising strategy for tumor treatment. Still, its therapeutic efficacy is compromised by the unsatisfactory cytotoxicity to specific subcellular organelles and insidious tumor microenvironment properties like hypoxia and high glutathione levels. Here, we fabricated a novel nanoenzyme that derived from metal-organic framework (MOF) with intrinsic catalase-like activities to decompose H2O2 to O2 and simultaneous glutathione consumption for enhancing PDT efficacy. The obtained Mn3O4 nanoparticle shows a larger pore size and surface area compared to native MOF particles, which can be used to load high dose photosensitizer. When decorated with AS1411 aptamer and polyethylene glycol (PEG), the obtained Mn3O4-PEG@C&A particle exhibits excellent stability and cell nucleus targeting ability. Remarkably, Mn3O4-PEG@C&A particle inhibited the tumor growth in the mouse model with high efficacy without any biotoxicity. This is the first report that applied MOF-derived nanoparticle to nucleus-targeted PDT. It may provide a new approach for designing functional nanoenzyme to subcellular organelles-targeted tumor modulation.

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Acknowledgements

We gratefully acknowledge the financial support from National Natural Science Foundation of China (Nos. 21775049, 31700746, 31870856 and 31870854) and National Key R&D Program of China (Nos. 2017YFA0700403 and 2016YFF0100801) and China Postdoctoral Science Foundation funded project (Nos. 2018M630847 and 2018T110753).

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  1. Xuemei Zeng and Shuangqian Yan contributed equally to this work.

Authors and Affiliations

  1. The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China

    Xuemei Zeng, Shuangqian Yan, Peng Chen, Wei Du & Bi-Feng Liu

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  1. Xuemei Zeng
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  2. Shuangqian Yan
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Correspondence to Bi-Feng Liu.

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12274_2020_2746_MOESM1_ESM.pdf

Modulation of tumor microenvironment by metal-organic-framework-derived nanoenzyme for enhancing nucleus-targeted photodynamic therapy

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Zeng, X., Yan, S., Chen, P. et al. Modulation of tumor microenvironment by metal-organic-framework-derived nanoenzyme for enhancing nucleus-targeted photodynamic therapy. Nano Res. 13, 1527–1535 (2020). https://doi.org/10.1007/s12274-020-2746-4

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