X-ray preactivated reversible persistent luminescence enables photodynamic immunotherapy of deep tumors

Persistent luminescence is a promising approach for photodynamic therapy (PDT) in deep-seated tumors, as it provides sustained light within tissues, eliminating the need for continuous external illumination. However, the uncontrollability of light within the body complicates precise spatiotemporal regulation. In this study, we report X-ray preactivated elimusertib-loaded tumor-targeted photodynamic nanoparticles (ETPNs), featuring reversible “on-off” afterglow properties. The excellent afterglow properties of X-ray-activated porous NaYF4:Er@NaGdF4 persistent luminescence nanoparticles enable the continuous activation of chlorin e6 (Ce6) to generate reactive oxygen species (ROS), leading to DNA damage. The integration of elimusertib potentiates ROS-induced DNA damage and activates the cGAS-STING pathway, thereby enhancing immuno-photodynamic therapeutic efficacy. All in vivo experiments were conducted using female mice. Our findings highlight the potential of ETPNs to advance the therapeutic landscape for deep-seated tumors, offering a robust and controllable platform for combined immuno-photodynamic therapy. Persistent luminescence is promising for photodynamic therapy in deep-seated tumors, but the uncontrollability of light within the body complicates precise spatiotemporal regulation. Here, the authors report X-ray preactivated elimusertib-loaded tumor-targeted photodynamic nanoparticles with controllable “on-off-on” afterglow properties for the treatment of deep-seated tumors.