Upconversion Composite Nanoparticles for Tumor Hypoxia Modulation and Enhanced Near-Infrared-Triggered Photodynamic Therapy

The efficacy of the conventional photodynamic therapy (PDT) is markedly suppressed by limited penetration depth of light in biological tissues and oxygen depletion in the hypoxic tumor microenvironment. Herein, mesoporous silica nanospheres with fine CaF2:Yb,Er upconversion nanocrystals entrapped in their porous structure are synthesized via a thermal decomposition method. After subsequently coating with a thin MnO2 layer and loading with a photosensitizer, Chlorin e6 (Ce6), a new type of nanoscale PDT platform is obtained. Within such composite nanoparticles, Mn2+ ions doped into the lattice of CaF2 crystals effectively enhance the near-infrared (NIR)-triggered red-light upconversion photoluminescence for exciting the adsorbed Ce6 via resonance energy transfer, enabling the improved photodynamic phenomenon. Meanwhile, the MnO2 coating modulates the hypoxic tumor microenvironment by in situ generating O2 through the reaction with tumor endogenous H2O2. Both mechanisms acting synchronously lead to the superior therapeutic outcome in NIR-triggered photodynamic tumor therapy.