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Spatially asymmetric cascade nanocatalysts for enhanced chemodynamic therapy

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Abstract

Chemodynamic therapy (CDT) based on cascade catalytic nanomedicine has emerged as a promising cancer treatment strategy. However, most of the reported cascade catalytic systems are designed based on symmetric- or co-assembly of multiple catalytic active sites, in which their functions are difficult to perform independently and may interfere with each other. Especially in cascade catalytic system that involves fragile natural-enzymes, the strong oxidation of free-radicals toward natural-enzymes should be carefully considered, and the spatial distribution of the multiple catalytic active sites should be carefully organized to avoid the degradation of the enzyme catalytic activity. Herein, a spatially-asymmetric cascade nanocatalyst is developed for enhanced CDT, which is composed by a Fe3O4 head and a closely connected mesoporous silica nanorod immobilized with glucose oxidase (mSiO2-GOx). The mSiO2-GOx subunit could effectively deplete glucose in tumor cells, and meanwhile produce a considerable amount of H2O2 for subsequent Fenton reaction under the catalysis of Fe3O4 subunit in the tumor microenvironment. Taking the advantage of the spatial isolation of mSiO2-GOx and Fe3O4 subunits, the catalysis of GOx and free-radicals generation occur at different domains of the asymmetric nanocomposite, minimizing the strong oxidation of free-radicals toward the activity of GOx at the other side. In addition, direct exposure of Fe3O4 subunit without any shelter could further enhance the strong oxidation of free-radicals toward objectives. So, compared with traditional core@shell structure, the long-term stability and efficiency of the asymmetric cascade catalytic for CDT is greatly increased by 138%, thus realizing improved cancer cell killing and tumor restrain efficiency.

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Acknowledgements

This work is supported by the National Natural Science Foundation of China (Nos. 22075049, 21875043, 22088101, 21701027, 21733003, 21905052, and 51961145403), the National Key R&D Program of China (Nos. 2018YFA0209401 and 2018YFE0201701), Key Basic Research Program of Science and Technology Commission of Shanghai Municipality (No. 17JC1400100), Natural Science Foundation of Shanghai (Nos. 22ZR1478900, 18ZR1404600, and 20490710600), Fundamental Research Funds for the Central Universities (20720220010), Shanghai Rising-Star Program (No. 20QA1401200). The authors express their gratitude to Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2023R55), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia. The statements made herein are solely the responsibility of the authors.

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  1. Minchao Liu and Hongyue Yu contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, iChem, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai, 200433, China

    Minchao Liu, Hongyue Yu, Liang Chen, Tiancong Zhao, Mengli Liu, Qiaoyu Zhou, Fan Zhang, Dongyuan Zhao & Xiaomin Li

  2. Department of Musculoskeletal Cancer Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Meng Fang

  3. Department of Physics, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia

    Fatemah Farraj AlHarbi

  4. King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, 11451, Saudi Arabia

    Ahmed Mohamed El-Toni

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  1. Minchao Liu
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Correspondence to Xiaomin Li.

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Liu, M., Yu, H., Chen, L. et al. Spatially asymmetric cascade nanocatalysts for enhanced chemodynamic therapy. Nano Res. 16, 9642–9650 (2023). https://doi.org/10.1007/s12274-023-5486-4

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