Highly Emissive Dye-Sensitized Upconversion Nanostructure for Dual-Photosensitizer Photodynamic Therapy and Bioimaging

Rare-earth-based upconversion nanotechnology has recently shown great promise for photodynamic therapy (PDT). However, the NIR-induced PDT is greatly restricted by overheating issues on normal bodies and low yields of reactive oxygen species (ROS, ¹O₂). Here, IR-808-sensitized upconversion nanoparticles (NaGdF₄:Yb,Er@NaGdF₄:Nd,Yb) were combined with mesoporous silica, which has Ce6 (red-light-excited photosensitizer) and MC540 (green-light-excited photosensitizer) loaded inside through covalent bond and electrostatic interaction, respectively. When irradiated by tissue-penetrable 808 nm light, the IR-808 greatly absorb 808 nm photons and then emit a broadband peak which overlaps perfectly with the absorption of Nd³⁺ and Yb³⁺. Thereafter, the Nd³⁺/Yb³⁺ incorporated shell synergistically captures the emitted NIR photons to illuminate NaGdF₄:Yb,Er zone and then radiate ultrabright green and red emissions. The visible emissions simultaneously activate the dual-photosensitizer to produce a large amount of ROS and, importantly, low heating effects. The in vitro and in vivo experiments indicate that the dual-photosensitizer nanostructure has trimodal (UCL/CT/MRI) imaging functions and high anticancer effectiveness, suggesting its potential clinical application as an imaging-guided PDT technique.