Rose Bengal Decorated NaYF 4 :Tb Nanoparticles for Low Dose X-ray-Induced Photodynamic Therapy in Cancer Cells.

The use of scintillating nanoparticles (ScNPs) in X-ray-induced photodynamic therapy (X-PDT) is a technique for deep tissue-localized tumor therapy with few side effects. ScNPs transfer X-ray-induced energy to photosensitizers, which generate massive amounts of reactive oxygen species (ROS) and kill cancer cells. Here we fabricated rose bengal (RB)-installed, Tb-rich NaYF nanocrystals (NaYF:Tb@RB), in which optically inert Y enables highly efficient energy transfer via high amounts of Tb doping. NaYF:Tb was prepared via solvothermal synthesis to have an average size of 7.6 nm, followed by coating with poly(maleic anhydride--1-octedecene)-poly(ethylene glycol) with a molecular weight of 2000 (CPMH-PEG). Further, RB was covalently conjugated to carboxyl groups generated from PMH on NaYF:Tb using an ethylenediamine linker. NaYF:Tb@RB exhibited a hydrodynamic diameter of ∼75 nm with a ζ-potential of -12 mV. NaYF:Tb@RB efficiently generated ROS in cultured luciferase-expressing murine epithelial breast cancer (4T1-luc) cells under low dose X-ray irradiation (0.5 Gy). The ROS generation amounts of NaYF:Tb@RB were 1.5-2-fold higher than those of NaGdF:Tb@RB, in which host nanocrystals were prepared with optically active Gd. Flow cytometric and confocal microscopic analyses showed higher intracellular ROS production of NaYF:Tb@RB, compared to NaYF:Tb and RB, resulting in higher X-ray-induced DNA damage in cultured 4T1-luc cells. Ultimately, NaYF:Tb@RB elicited significant cytotoxicity after X-ray irradiation (0.5 Gy), while inducing marginal cytotoxicity without X-ray irradiation. Altogether, this research proposes a promising ScNP design for efficient X-PDT agents that make the better use of incident X-ray energy while causing the fewest side effects.