Synthesis of lanthanide-based scintillator@MOF nanocomposites for X-ray-induced photodynamic therapy

Multifunctional nanocomposites comprising a set of diverse nanoparticles are highly desirable for realizing on-demand therapy with minimized adverse effects. X-ray-induced photodynamic therapy (X-PDT) has reformed conventional PDT for deep-seated tumors by using penetrating X-rays, but its application faces the challenge of efficiently integrating scintillators with photosensitizers. In this study, core-shell nanocomposites rationally integrating NaGdF4:Tb@NaGdF4:Ce@NaLuF4 nanoparticles with Hf-porphyrin metal-organic frameworks (MOFs) using a surface-assisted epitaxial growth strategy have been proposed and synthesized. Herein, NaGdF4:Tb@NaGdF4:Ce@NaLuF4 nanoparticles demonstrate strong X-ray attenuation and bright green light emissions, serving as efficient scintillators to activate the photosensitizer. The porphyrin in MOFs can absorb and be further activated by the emission of a lanthanide-based scintillator, playing the role of a photosensitizer to generate a significant amount of singlet oxygen. Moreover, uniform nanocomposites with regular core-shell structures enable the maximization of energy transfer between the scintillator and MOFs, and the inherent pores of MOFs facilitate the diffusion of reactive oxygen species (ROS) out of the interior to boost PDT efficacy. In addition, the existence of heavy atoms such as Gd, Lu, and Hf can significantly enhance radiation sensitization, facilitating the production of hydroxyl radicals. This work presents a novel strategy for fabricating lanthanide-based scintillator@MOF nanocomposites for efficient X-PDT and is anticipated to promote theranostic applications of nanocomposites. Nanocomposites were proposed and fabricated to simultaneously generate singlet oxygen (1O2) through energy transfer from SNPs to Hf-TCPP and hydroxyl radicals (OH) by the introduction of high-Z elements under low-dose X-ray irradiation.