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Necroptosis-elicited host immunity: GOx-loaded MoS2 nanocatalysts for self-amplified chemodynamic immunotherapy

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Abstract

Nanoparticles induced potent antitumor immunotherapy plays a significant role for enhancing conventional therapeutic effectiveness. However, revealing the pathway of how nanoagents themselves trigger the host immunity or how to maximize the immunotherapy efficacy still needs further exploration. Herein, rose-like MoS2 nanoflowers modified with 2-deoxy-D-glucose (2-DG) and glucose oxidase (GOx) (MPGGFs) have been successfully fabricated via a one-pot hydrothermal reaction and following one-by-one surface modification as a multifunctional nanocatalyst for photothermal therapy enhanced self-amplified chemodynamic immunotherapy (PTT-co-CDT). By introducing GOx, the obtained MPGGFs exhibited self-amplified chemodynamic therapeutic efficacy under hypoxia tumor microenvironment (TME) because of the raised intracellular H2O2 level via enzyme-catalysis of oxygen. Furthermore, combined with the intrinsic excellent photothermal conversion efficiency of MoS2 nanoflowers, PTT-co-CDT performances by MPGGFs could effectively induce the necroptosis of tumor cells both in vitro and in vivo. Then the induced necroptosis via PTT-co-CDT by MPGGFs could directly trigger host immunity by activating the antigen-specific T-cells (CD4+ and CD8+). Finally, the excellent in vivo safety of MPGGFs makes us believe that the successful construction of rose-like multifunctional nanocatalyst not only has great potentials for self-amplified chemodynamic immunotherapy, but also provides a paradigm for exploring necroptosis triggered host immunity for cancer treatment.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81671829, 21788102, and 51971116). Many thanks to Hunan Provincial Innovation Foundation for Postgraduate (No. 2020zzts079). By the way, all authors have given approval to the final version of the manuscript.

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  1. Wensheng Xie

    Present address: Present address: Department of Chemistry, Tsinghua University, Beijing, 100084, China

Authors and Affiliations

  1. The Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China

    Wensheng Xie & Yen Wei

  2. State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China

    Wensheng Xie, Jingsong Lu, Zhenhu Guo, Xiaoxiao Guo, Yongjiu Chi, Jieling Ye, Junxin Zhang, Wanling Xu & Lingyun Zhao

  3. Research Center of Magnetic and Electronic Materials, College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou, 310014, China

    Jingsong Lu

  4. State Key Laboratory of Powder Metallurgy, Powder Metallurgy Research Institute, Central South University, Changsha, 410083, China

    Zhenhu Guo

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  1. Wensheng Xie
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Correspondence to Lingyun Zhao or Yen Wei.

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Xie, W., Lu, J., Guo, Z. et al. Necroptosis-elicited host immunity: GOx-loaded MoS2 nanocatalysts for self-amplified chemodynamic immunotherapy. Nano Res. 15, 2244–2253 (2022). https://doi.org/10.1007/s12274-021-3763-7

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