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

Photothermal therapy (PTT) has emerged as a promising strategy for the treatment of tumors. However, the intrinsic self-repair mechanism of cells and the nonspecific photothermal effect of photothermal agents can result in poor treatment outcomes and normal tissue injury. To address this issue, we developed a dual light activatable perylenediimide derivative (P-NO) for nitric oxide-enhanced PTT. P-NO can self-assemble into nanoparticles in aqueous solutions. The P-NO nanoparticles are capable of releasing both NO and a photothermal molecule (P-NH) upon green light irradiation. The simultaneous release of NO and P-NH activates the photothermal effect and inhibits cell protection autophagy, thereby improving the therapeutic efficacy of PTT under near-infrared (NIR) light. Moreover, the switch on of NIR fluorescence allows real-time monitoring of the release of P-NH. Remarkably, in a mouse subcutaneous tumor model, significant tumor ablation can be achieved following dual light activated photothermal gas therapy. This work offers a promising and straightforward approach to constructing activatable perylenediimide-based photothermal agents for enhancing the effectiveness of photothermal gas therapy.