Rare Earth-Doped Nanoparticles for Near-Infrared II Image-Guided Photodynamic Therapy

Image-guided disease treatment not only significantly enhances the efficacy of disease treatment but also minimizes unnecessary medication doses. Near-infrared II (NIR-II, 1000-1700 nm) bioimaging has been considered as one of the ideal bioimaging techniques in recent years due to its deep tissue penetration and low tissue fluorescence scattering. Here, we design the highly biocompatible lanthanide-doped nanoparticles NaYF₄:Ce/Er@NaYbF₄:Er@NaYF₄:Nd-ZnPc/RB/mPEG-FA (RENPs-ZnPc/RB/mPEG-FA). Under an 808 nm excitation, the internal rare earth-doped nanoparticles (RENPs) can emit NIR-II luminescence for imaging. In addition, the generated upconversion luminescence in the visible region can be used as an excitation light source to excite the photosensitizers on the surface of the RENPs to generate singlet oxygen for antitumor photodynamic therapy. Based on the guidance of NIR-II imaging, the intratumoral injection approach is selected. During the treatment (day 7) after the second dose of RENPs-ZnPc/RB/mPEG-FA injection, the tumors are almost inhibited and eliminated, and there is no sign of recurrence in the follow-up observations. Interestingly, intravenously injected nanoparticles also enable high-resolution skeletal imaging with a high signal-to-background ratio, which holds promise for the clinical translation of RENPs-ZnPc/RB/mPEG-FA as versatile probes for imaging and therapy.