Enhancing Luminescence in Lanthanide-Doped Fluoride Nanoparticles via Oil-Thermal Annealing Strategy for Efficient X-ray-Excited Photodynamic Therapy

Abstract

X-ray excited photodynamic therapy (X-PDT), a synergistic therapy combining radiotherapy (RT) with photodynamic therapy (PDT), not only demonstrates more effective therapeutic outcomes but also overcomes the limitation of PDT’s shallow penetration depth. Lanthanide-doped fluoride nanoparticles exhibit excellent X-ray excitation optical luminescence (XEOL), tunable luminescence, and favorable biosafety, making them promising for X-ray excited photodynamic therapy (X-PDT). However, excessive surface defects in nanoparticles diminish luminescence efficiency and quench XEOL, significantly compromising the efficacy of X-PDT. Here, we report an oil-thermal annealing strategy to obtain small-sized nanocrystals with strong luminescence by repairing surface defects and improving the luminescence intensity while keeping the particle morphology and size. Specifically, the XEOL intensity of NaYF₄:Er@NaYF₄ core–shell nanocrystals is enhanced by about 11.6 times compared to the pristine NaYF₄:Er core nanocrystals after Y/Na oil-thermal annealing treatment. This demonstrates that the oil-thermal annealing treatment is able to remodel the surface lattice structure, effectively inhibiting nonradiative recombination and improving crystallinity. Water-soluble modification of annealed NaYF₄:Er@NaYF₄ core–shell nanocrystals via 2-aminoethylphosphonic acid (AEP) ligand exchange and loading Rose Bengal (RB) photosensitizer showed good antitumor efficacy against CT26 cancer cells in vitro and in vivo, with an in vivo tumor inhibition rate of 87.6% and no side effects. This study provides insight into the future synthesis and luminescence enhancement of high-performance X-ray excited luminescent nanoparticles and their role in reducing side effects and enhancing therapeutic efficacy in X-PDT applications.