Targeted Photoredox System under a Hypoxic Environment to Evoke Photodynamic Immunotherapy

Area of Science:

• Materials Science
• Biomedical Engineering
• Photochemistry

Background:

• Photodynamic therapy (PDT) efficacy is limited by tumor hypoxia.
• Type-I photosensitizers (PSs) offer an alternative due to reduced oxygen dependence.
• A clear design strategy for Type-I PSs is lacking.

Purpose of the Study:

• To synthesize and evaluate a novel Type-I PS (BDP-Ir-bpt) for cancer therapy.
• To investigate the mechanism of action under hypoxic conditions.
• To assess the potential for photodynamic immunotherapy.

Main Methods:

• Synthesis of BDP-Ir-bpt with modified triplet state energy.
• In vitro studies under hypoxia with 630 nm irradiation.
• Analysis of intracellular reactive oxygen species (ROS) production.
• Investigation of lysosomal membrane rupture and pyroptosis induction.
• In vivo evaluation in a mouse prophylactic model.

Main Results:

• BDP-Ir-bpt successfully generated intracellular O₂^-• and •OH under hypoxia.
• Photodynamic treatment disrupted the intracellular photoredox system.
• Lysosomal membrane rupture and GSDMD-mediated pyroptosis were induced.
• Innate immune responses were evoked in vivo.
• The synthesized PS relieved the hypoxic microenvironment.

Conclusions:

• BDP-Ir-bpt is a promising Type-I PS for overcoming tumor hypoxia.
• The study highlights the importance of rational structural design for PS development.
• This work demonstrates a strategy for photodynamic immunotherapy via ROS generation and pyroptosis induction.