Near-Infrared-II-Activated Transition Metal(II)-Coordinated Ligand Radical Primes Robust Anticancer Immunity

Area of Science:

• Biomedical Engineering
• Materials Science
• Cancer Therapy

Background:

• Photoactivatable metallodrugs offer targeted cancer therapy by combining tumor cell eradication and immune stimulation.
• Current limitations include oxygen dependence, narrow visible light responsiveness, and poor immunogenicity, hindering efficacy in deep, hypoxic, and immunosuppressive tumors.

Purpose of the Study:

• To design novel transition metal(II)-coordinated ligand radicals for enhanced cancer therapy.
• To address limitations of existing photoactivatable metallodrugs, focusing on oxygen independence and near-infrared-II (NIR-II) light activation.

Main Methods:

• Development of cobalt(II)-coordinated ligand radical (BPDP-Co) with intense NIR-II absorption.
• Evaluation of oxygen-independent photothermal performance and endoplasmic reticulum-targeting capability.
• Assessment of BPDP-Co efficacy in inducing pyroptosis and releasing damage-associated molecular patterns (DAMPs) and proinflammatory cytokines under normoxic and hypoxic conditions upon 1064 nm laser irradiation.

Main Results:

• BPDP-Co demonstrated intense NIR-II absorption and oxygen-independent photothermal performance.
• 1064 nm laser irradiation of BPDP-Co induced highly immunogenic pyroptosis in tumor cells, even under severe hypoxia.
• In vivo studies showed significant inhibition of 4T1 tumor growth (85.7% inhibition rate) in mice, indicating a robust antitumor immune response.

Conclusions:

• The developed cobalt(II)-coordinated ligand radical (BPDP-Co) effectively overcomes limitations of traditional photoactivatable metallodrugs.
• NIR-II activation of BPDP-Co shows potent therapeutic potential for targeted cancer therapy and immunotherapy, particularly in challenging tumor microenvironments.
• This strategy holds promise for advancing photothermal therapy and cancer immunotherapy through novel metallodrug design.