Electron Donors Rather Than Reactive Oxygen Species Needed for Therapeutic Photochemical Reaction of Near-Infrared Photoimmunotherapy

Near-infrared photoimmunotherapy (NIR-PIT) employs molecularly targeted antibodies conjugated with a photoabsorbing silicon-phthalocyanine dye derivative which binds to cancer cells. Application of NIR light following binding of the antibody-photoabsorber conjugates (APCs) results in ligand release on the dye, dramatic changes in solubility of the APC-antigen complex, and rapid, irreversible cell membrane damage of cancer cells in a highly selective manner, resulting in a highly immunogenic cell death. Clinically, this process results in edema after treatment mediated by reactive oxygen species (ROS). Based on the chemical and biological mechanism of NIR-PIT cytotoxicity and edema formation, in order to minimize acute inflammatory edema without compromising therapeutic effects, L-sodium ascorbate (L-NaAA) was administered to quench harmful ROS and accelerate the ligand release reaction. L-NaAA suppressed acute edema by reducing ROS after NIR-PIT yet did not alter the therapeutic effects. NIR-PIT could be performed safely under existence of L-NaAA without side effects caused by unnecessary ROS production.

Automated summary

NIR-PIT utilizes molecularly targeted antibodies with a photosensitive dye to target cancer cells, causing irreversible damage and highly immunogenic cell death through near-infrared light exposure. The use of L-NaAA can suppress acute edema, accelerate ligand release, and enhance therapeutic effects without causing side effects from unnecessary ROS production.