The exploitation of gas therapy platforms holds great promise as a "green" approach for selective cancer therapy, however, it is often associated with some challenges, such as uncontrolled or insufficient gas generation and unclear therapeutic mechanisms. In this work, a gas therapy approach based on near-infrared (NIR) light-triggered sulfur dioxide (SO2) generation was developed, and the therapeutic mechanism as well as in vivo antitumor therapeutic efficacy was demonstrated. A SO2 prodrug-loaded rattle-structured upconversion@silica nanoparticles (RUCSNs) was constructed to enable high loading capacity without obvious leakage and to convert NIR light into ultraviolet light so as to activate the prodrug for SO2 generation. In addition, SO2 prodrug-loaded RUCSNs showed high cell uptake, good biocompatibility, intracellular tracking ability, and high NIR light-triggered cytotoxicity. Furthermore, the cytotoxic SO2 was found to induce cell apoptosis accompanied by the increase of intracellular reactive oxygen species levels and the damage of nuclear DNA. Moreover, efficient inhibition of tumor growth was achieved, associated with significantly prolonged survival of mice. Such NIR light-triggered SO2 therapy may provide an effective strategy to stimulate further development of synergistic cancer therapy platforms.
Keywords: cancer therapy; gas therapy; near-infrared; sulfur dioxide; upconversion nanoparticles.