Translational Interfaces of Near-Infrared Photoimmunotherapy:

Near-infrared photoimmunotherapy (NIR-PIT) converts antibody-antigen binding into highly localized cytotoxicity through 690 nm light activation of an antibody-photoabsorber conjugate (APC). Distinct from photodynamic or photothermal modalities, NIR-PIT operates via photoinduced axial-ligand dissociation of IRDye700DX (IR700), which drives hydrophobic collapse, APC clustering on the plasma membrane, and rapid membrane disruption-termed photochemosis-without generating reactive oxygen species or causing bulk heating. Beyond immediate tumor debulking, NIR-PIT elicits immunogenic cell death (ICD) characterized by calreticulin exposure and ATP/HMGB1 release, and induces the super-enhanced permeability and retention (SUPR) effect that transiently increases intratumoral accumulation of macromolecules and nanodrugs by up to approximately 24-fold in particular in vivo models, compared with the baseline EPR effect. These distinct photochemical and immunological mechanisms provide a strong rationale for combinatorial strategies integrating NIR-PIT with immune checkpoint blockade, cytotoxic chemotherapy, nanomedicine, radiotherapy, and clinically relevant hyperthermia. This review summarizes the mechanistic basis of photochemosis, ICD, and SUPR, and discusses their translational applications, device innovations, and intersections with thermal biology, providing a conceptual framework for advancing photothermal-photoimmunological oncology.