Leveraging Vitamin C to Augment Nanoenabled Photothermal Immunotherapy

Area of Science:

• Oncology
• Immunology
• Biomedical Engineering

Background:

• Photothermal immunotherapy (PTI) shows promise for tumor targeting and immune activation.
• Efficacy is limited by insufficient immune response, tumor antioxidants, and resistance.
• Novel strategies are needed to enhance PTI effectiveness.

Purpose of the Study:

• To investigate Vitamin C (VC) as an enhancer for nanoenabled near-infrared-II photothermal therapy (NIR-II PTT).
• To evaluate the combined effect of VC and NIR-II PTT on antitumor immunity.
• To explore the clinical relevance of biomarkers associated with this combined therapy.

Main Methods:

• Utilized high-dose Vitamin C to induce oxidative imbalance in tumor cells.
• Employed nanoenabled near-infrared-II photothermal therapy (NIR-II PTT) with IR1080.
• Assessed changes in immune cell infiltration and cytokine expression (CXCL16).
• Analyzed clinical data correlating CXCL16 and CXCR6 levels with patient survival and T cell infiltration.

Main Results:

• High-dose VC sensitized tumor cells to NIR-II PTT.
• The combination therapy significantly amplified antitumor immunity.
• CXCL16 expression and CXCR6+ T cell infiltration were markedly upregulated.
• Clinical data supported the correlation between higher CXCL16/CXCR6 and improved outcomes.

Conclusions:

• Vitamin C is a safe, accessible, and cost-effective enhancer for PTI.
• Combining VC with NIR-II PTT overcomes tumor resistance and boosts antitumor immunity.
• This approach holds significant translational potential for cancer therapy.