A self-supplying H₂O₂ "nano-reaction engine" with photothermal boosting for cascade chemodynamic-immunotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy
• Immunotherapy

Background:

• Chemodynamic therapy (CDT) converts hydrogen peroxide (H2O2) to hydroxyl radicals (•OH) for tumor ablation.
• CDT efficacy is limited by low H2O2 levels and high glutathione (GSH) in the tumor microenvironment (TME), creating a protective redox state.
• Overcoming these barriers is crucial for enhancing CDT and tumor immunotherapy.

Purpose of the Study:

• To develop a self-supplying H2O2 nanoplatform (CZPI) for enhanced tumor immunotherapy.
• To integrate a photothermal booster with a chemodynamic reaction engine for synergistic cancer therapy.
• To overcome the intrinsic limitations of the tumor microenvironment for improved therapeutic outcomes.

Main Methods:

• Developed CZPI nanoplatform with a Cu-ZnO2 core and polydopamine (PDA)/indocyanine green (ICG) surface modification.
• Utilized acid-triggered decomposition of ZnO2 in the TME to release H2O2 and Cu2+.
• Employed Cu+/2+ redox cycling and Fenton-like reactions for continuous •OH production, amplified by photothermal effects from PDA/ICG under near-infrared (NIR) irradiation.

Main Results:

• CZPI effectively generated H2O2 and •OH in the TME, overcoming GSH-mediated resistance.
• The photothermal effect of PDA/ICG accelerated reaction kinetics and amplified •OH generation.
• CZPI induced apoptosis, ferroptosis, and immunogenic cell death (ICD), activating systemic anti-tumor immune responses.

Conclusions:

• The developed CZPI nanoplatform offers a novel 'reaction engine-booster' paradigm for synergistic cancer therapy.
• This approach effectively integrates self-supplying H2O2 generation with photothermal acceleration.
• CZPI shows potential as a powerful platform for multimodal synergistic cancer therapy and durable immune activation.