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

Abstract

Near-infrared photoimmunotherapy (NIR-PIT) is a cancer treatment modality that uses antibody-photoabsorber (IR700) conjugates to destroy specific cells. The reaction between the antibody and photoabsorber is triggered by NIR-light, and this alters the shape and hydrophilicity of the conjugate. This photochemical reaction is responsible for NIR-PIT-induced cell death; however, the detailed mechanism underlying this effect remains unknown. In this study, we demonstrated that actin filaments underneath the cell membrane play an important role in NIR-PIT-induced cell death and that IR700 mediates the photochemical reaction of the conjugates, leading to actin filament aggregation upon NIR-light irradiation. The destruction of cortical actin beneath the cell plasma membrane allows water to flow into the cell based on osmotic conditions, resulting in cell rupture. This sequence of events may constitute the mechanism of NIR-PIT-induced cell death, making NIR-PIT a promising cancer treatment modality.