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Immunomodulation-Enhanced Nanozyme-Based Tumor Catalytic Therapy.

Bolong Xu1, Yan Cui1,2, Weiwei Wang1

  • 1Beijing Advanced Innovation Center for Soft Matter Science and Engineering, State Key Laboratory of Organic-Inorganic Composites, Bionanomaterials & Translational Engineering Laboratory, Beijing Key Laboratory of Bioprocess, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China.

Advanced Materials (Deerfield Beach, Fla.)
|July 7, 2020
PubMed
Summary

This study introduces a novel nanozyme therapy that enhances cancer treatment by modulating the tumor microenvironment. The strategy boosts hydrogen peroxide levels, improving nanozyme efficacy for potent antitumor effects.

Keywords:
catalase-like activityimmunomodulationnanozymesperoxidase-like activitytumor catalytic therapy

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Nanozyme-based tumor catalytic therapy shows promise but is limited by the tumor microenvironment (TME).
  • Factors like low hydrogen peroxide (H₂O₂) concentration, hypoxia, and immunosuppression hinder therapeutic outcomes.
  • A synergistic approach combining nanozymes with TME regulation is needed.

Purpose of the Study:

  • To develop an immunomodulation-enhanced nanozyme strategy for improved cancer catalytic therapy.
  • To investigate the synergistic effects of nanozymes and TME regulation.
  • To create TGF-β inhibitor-loaded PEGylated iron manganese silicate nanoparticles (IMSN-PEG-TI) for enhanced cancer treatment.

Main Methods:

  • Constructed IMSN-PEG-TI nanoparticles loaded with a TGF-β inhibitor.
  • Evaluated the peroxidase-like and catalase-like activities of IMSN in acidic TME.
  • Assessed the immunomodulatory effects on macrophage polarization (M2 to M1).
  • Tested the antitumor efficacy in vitro using multicellular tumor spheroids (MCTS) and in vivo using CT26-tumor-bearing mice models.

Main Results:

  • IMSN demonstrated peroxidase-like and catalase-like activities, decomposing H₂O₂ into hydroxyl radicals and oxygen.
  • Both IMSN and the TGF-β inhibitor promoted M2 to M1 macrophage polarization.
  • This polarization regenerated H₂O₂, further enhancing IMSN's catalytic activity.
  • Significant antitumor effects were observed in both MCTS and in vivo models.

Conclusions:

  • The developed immunomodulation-enhanced nanozyme strategy shows significant potential for cancer therapy.
  • Synergism between nanozymes and TME regulation offers a promising approach to overcome therapeutic limitations.
  • IMSN-PEG-TI represents a viable tool for effective cancer cell killing.