Photoinduced Actin Aggregation Involves Cell Death: A Mechanism of Cancer Cell Cytotoxicity after Near-Infrared Photoimmunotherapy

Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer modality that uses antibody-photoabsorber IR700 conjugates to destroy specific cells. The reaction between the antibody and photoabsorber is triggered by NIR-light, altering the conjugate's shape and hydrophilicity. This photochemical reaction explains the starting point of cell death in NIR-PIT; however, its mechanism remains unknown. In this study, we demonstrated that actin filaments underneath the cell membrane play an important role in the cell death mechanism of NIR-PIT, and the photochemical reaction of the IR700 photo-absorber of the conjugates led to actin filament aggregation with NIR-light irradiation. The destruction of cortical actin beneath the plasma cell membrane allows water to flow inside the cell according to the osmotic conditions, resulting in cell rupture. This sequence of events may be the cell death mechanism of NIR-PIT, which makes NIR-PIT a unique modality.