Terbium-Rose Bengal Coordination Nanocrystals-Induced ROS Production under Low-Dose X-rays in Cultured Cancer Cells for Photodynamic Therapy

초록

X-ray-triggered scintillators (Sc) and photosensitizers(Ps) havebeen developed for X-ray-induced photodynamic therapy (X-PDT) to selectivelydestruct deep tissue tumors with a low X-ray dose. This study designedterbium (Tb)-rose bengal (RB) coordination nanocrystals (T-RBNs) bya solvothermal treatment, aiming to reduce photon energy dissipationbetween Tb3+ and RB and thus increase the reactive oxygenspecies (ROS) production efficiency. T-RBNs synthesized at a molarratio of [RB]/[Tb] = 3 exhibited a size of 6.8 +/- 1.2 nm witha crystalline property. Fourier transform infrared analyses of T-RBNsindicated successful coordination between RB and Tb3+.T-RBNs generated singlet oxygen (O-1(2)) and hydroxylradicals ((OH)-O-center dot) under low-dose X-ray irradiation(0.5 Gy) via scintillating and radiosensitizing pathways. T-RBNs produced similar to 8-fold higher ROS amounts than bare RB and similar to 3.6-foldhigher ROS amounts than inorganic nanoparticle-based controls. T-RBNsdid not exhibit severe cytotoxicity up to 2 mg/mL concentration incultured luciferase-expressing murine epithelial breast cancer (4T1-luc)cells. Furthermore, T-RBNs were efficiently internalized into cultured4T1-luc cells and induced DNA double strand damage, as evidenced byan immunofluorescence staining assay with phosphorylated gamma-H(2)AX. Ultimately, under 0.5 Gy X-ray irradiation, T-RBNs induced>70% 4T1-luc cell death via simultaneous apoptosis/necrosis pathways.Overall, T-RBNs provided a promising Sc/Ps platform under low-doseX-PDT for advanced cancer therapy.

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