Immunomodulation-Enhanced Nanozyme-Based Tumor Catalytic Therapy

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.