Reactive oxygen species generation by photothermal effects of adhesive near-infrared agents on the plasma membrane

Near-infrared photothermal cancer therapy has attracted increasing attention due to its non-invasiveness, high selectivity, and spatiotemporally controllable local treatment. A novel near-infrared photothermal agent was developed, consisting of a plasma membrane-adhesive indocyanine green conjugated with a polycation bearing quaternary ammonium salt groups, called adhesive indocyanine green, for locally administered near-infrared photothermal cancer therapy. In this study, the photothermal effects of adhesive indocyanine green on the plasma membrane were investigated using a rat gastric mucosal cancer cell line. Upon light irradiation, adhesive indocyanine green exhibited a photothermal effect without generating singlet oxygen. Due to electrostatic interaction, adhesive indocyanine green adhered to negatively charged polysaccharides on the plasma membrane of rat gastric mucosal cancer cells. When the cells were irradiated with near-infrared light at 808 ‍nm at 108 ‍J/cm², levels of intracellular reactive oxygen species significantly increased despite the absence of a detectable temperature rise in the cell culture medium. These results indicate the generation of intracellular reactive oxygen species by the photothermal effects of plasma membrane-adhesive near-infrared photothermal agents.