Amplifying oxidative stress utilizing multiband luminescence of lanthanide nanoparticles for eliciting systemic antitumor immunity

Reactive oxygen species (ROS) are closely related to innate and adaptive immune responses in tumor immunotherapy. ROS-mediated therapies show great hope in improving therapeutic efficacy by inducing immunogenic cell death. However, the efficiency is still limited by the poor ROS production rate. Herein, a ROS nanogenerator is designed to boost antitumor immunity, integrating with pH-dissociable Fe 3+ -gallic acid (Fe-GA) complex as the shell and photosensitizer (Chlorin e6, Ce6)-coupled lanthanide-doped luminescence nanoparticles (LnNPs) as the core. Upon near-infrared (NIR) light irradiation, LnNPs exhibit multiband upconversion emission from ultraviolet (UV) to visible (Vis) and downshifting emission in the promising second NIR imaging region (NIR-II, 1550 nm). Especially, the UV photons and reducing agent GA could respectively mediate the reduction of Fe 3+ , allowing more Fe 2+ to participate in the Fenton reaction to generate hydroxyl radicals (•OH) for ferroptosis therapy (FT). Besides, the UV–Vis upconversion emission can activate the coupling photosensitizer-Ce6 to generate 1 O 2 for photodynamic therapy (PDT). Additionally, Fe-GA can serve as a photothermal therapy (PTT) agent; in turn, hyperthermia enhances ROS generation. Our rational-designed [email protected] NPs could not only enhance the synergistic antitumor efficiency by boosting ROS generation but also effectively inhibit tumor metastasis by activating strong antitumor immunity, providing a paradigm for imaging-guided cancer treatment.