Oxygen-Independent Radiodynamic Therapy: Radiation-Boosted Chemodynamics for Reprogramming the Tumor Immune...

Area of Science:

• Nanotechnology
• Oncology
• Immunotherapy

Background:

• Radiodynamic therapy (RDT) shows promise for cancer treatment due to deep tissue penetration and radical generation.
• Hypoxic tumor conditions limit RDT efficacy by hindering oxygen-dependent radical production and immune cell modulation.
• Radioresistant immune suppression cells pose a significant challenge in cancer therapy.

Purpose of the Study:

• To develop an oxygen-independent RDT strategy to overcome hypoxic limitations in cancer treatment.
• To investigate the efficacy of a novel Fe12-polyoxometalate (POM) cluster for enhanced chemodynamic catalysis.
• To evaluate the combined effects of oxygen-independent RDT and PD-1 therapy on tumor immune microenvironment and abscopal effects.

Main Methods:

• Synthesis of a "super" tetrahedron Fe12-POM cluster with P2W15 energy antennas and an Fe3 catalytic core.
• Irradiation of the Fe12-POM cluster with X-rays to induce metal-to-metal charge transfer and enhance hydroxyl radical generation.
• Combination therapy involving Fe12-POM-mediated RDT and PD-1 immunotherapy in a mouse tumor model.

Main Results:

• X-ray irradiation of Fe12-POM resulted in a 139-fold increase in hydroxyl radical generation via Fe3+ to Fe2+ valence transition.
• The treatment reprogrammed the tumor immune microenvironment, upregulating CD80/86 and downregulating CD163 and FAP.
• Significant regression of both local and distant tumors was observed, indicating abscopal effects.
• Enhanced release of interferon-γ and tumor necrosis factor-α was detected.

Conclusions:

• Oxygen-independent RDT using Fe12-POM is a viable strategy to combat hypoxic tumors.
• The developed RDT approach effectively reprograms the tumor immune microenvironment, enhancing anti-tumor immunity.
• This novel RDT combined with immunotherapy holds potential for improving cancer treatment outcomes and addressing recurrence.