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

Photoactivatable metallodrugs combining tumor cell eradication
and immune stimulation hold immense promise for targeted cancer therapy.
However, limitations such as oxygen dependence, narrow visible light
responsiveness, and poor immunogenicity hinder their efficacy in deep
solid tumors with hypoxic and immunosuppressive microenvironments.
Herein, we present a novel design strategy for transition metal(II)-coordinated
ligand radicals exhibiting intense near-infrared-II (NIR-II) absorption,
unique endoplasmic reticulum-targeting capability, and oxygen-independent
photothermal performance, effectively addressing these constraints.
Proof-of-concept results demonstrate the potent efficacy of our cobalt(II)-coordinated
ligand radical (BPDP-Co) in inducing highly immunogenic
pyroptosis in tumor cells under both normoxic and severe hypoxic conditions
upon 1064 nm laser irradiation. This NIR-II activation triggers the
release of damage-associated molecular patterns (DAMPs) and proinflammatory
cytokines, fueling a robust antitumor immune response. In
vivo studies demonstrate that treatment with BPDP-Co/NIR-II significantly inhibited 4T1 tumor growth in BALB/c mice with
a high inhibitory rate of 85.7%, highlighting its therapeutic potential
in tumor immunotherapy.