Amplifying Anti-Tumor Immune Responses via Mitochondria-Targeting Near-Infrared Photodynamic Therapy

Area of Science:

• Oncology
• Immunology
• Materials Science

Background:

• Pro-inflammatory photodynamic therapy (PDT) shows promise for systemic anti-tumor immunity.
• Limited UV-visible light penetration and tumor hypoxia hinder conventional PDT efficacy.
• Novel strategies are needed to overcome these limitations for enhanced cancer treatment.

Purpose of the Study:

• To develop a mitochondria-targeting nanoplatform for near-infrared (NIR) light-activated PDT.
• To enhance systemic anti-tumor immunity and overcome challenges of deep-seated tumors and hypoxia.
• To improve the efficacy of immune checkpoint blockade (ICB) therapy.

Main Methods:

• A mitochondria-targeting nanoplatform (NZ@TG) was designed for NIR-activated PDT.
• The nanoplatform utilizes lanthanide-organic triplet photosensation for localized oxidative damage.
• PDT-induced hypoxia activates a TH302 prodrug, leading to cell cycle arrest and immunogenic cell death (ICD).

Main Results:

• The nanoplatform demonstrated enhanced tumor ablation in deep-seated lesions in orthotopic liver tumor models.
• It successfully triggered ICD, releasing damage-associated molecular patterns (DAMPs) to activate immune responses.
• Significant long-term anti-tumor immune memory was induced, improving ICB therapy efficacy.

Conclusions:

• The developed NIR-PDT nanoplatform effectively addresses limitations of conventional PDT for deep-seated tumors.
• This strategy robustly activates anti-tumor immunity, offering a promising approach for cancer therapy.
• The approach holds potential for preventing tumor recurrence and enhancing combination therapies.