Spatiotemporal control of photothermal heating using pH sensitive near-infrared croconaine-based dyes

Near-infrared (NIR) absorbing dyes sensitive to pH are promising small molecules that can be used in photothermal therapy for intracellular cancer treatment. In this study, a croconaine dye molecule protected within a macrocycle has been prepared to be tested as photothermic agent. This pH sensitive croconaine dye allowed a selective NIR-light absorption only when the molecule was located in an acidic environment like the one found in intracellular vesicles; meanwhile it remained inactivated under physiological conditions. Results showed that photothermic heating produced upon 808 nm laser irradiation on mouse melanoma cells treated with this croconaine-based dye resulted in cell death which may be attributed to a dye uptake into acidic intracellular vesicles (i.e., endosomal-lysosomal pathway). Cell damage was exclusively produced on irradiated cells, without any damage observed in neighboring cells. Negligible reactive oxygen species release was detected, thus the effect was attributed to a pure photothermic process. Croconaine dye presented a subcytotoidc concentration of 100 mu M on macrophages and tumoral cells. From the results obtained it can be concluded than these types of near-infrared dyes have shown great promise as photothermal agents, providing a great opportunity for achieving a spatiotemporal control on photothermal cancer therapy.