Perylenediimides with Enhanced Autophagy Inhibition for a Dual-Light Activatable Photothermal Gas Therapy

Photothermal therapy (PTT) has emerged as a promisingstrategyfor the treatment of tumors. However, the intrinsic self-repair mechanismof cells and the nonspecific photothermal effect of photothermal agentscan result in poor treatment outcomes and normal tissue injury. Toaddress this issue, we developed a dual light activatable perylenediimidederivative (P-NO) for nitric oxide-enhanced PTT. P-NO can self-assembleinto nanoparticles in aqueous solutions. The P-NO nanoparticles arecapable of releasing both NO and a photothermal molecule (P-NH) upongreen light irradiation. The simultaneous release of NO and P-NH activatesthe photothermal effect and inhibits cell protection autophagy, therebyimproving the therapeutic efficacy of PTT under near-infrared (NIR)light. Moreover, the switch on of NIR fluorescence allows real-timemonitoring of the release of P-NH. Remarkably, in a mouse subcutaneoustumor model, significant tumor ablation can be achieved following dual light activated photothermal gas therapy. This work offers apromising and straightforward approach to constructing activatableperylenediimide-based photothermal agents for enhancing the effectivenessof photothermal gas therapy.