Dual-Mode T1/T2MRI Contrast Agent Based on LuGdF ₃ Nanoparticles for Enhancement of X-ray Induced Cancer Radiotherapy

Nanoparticles-mediated radiosensitization is one of the most promising ways to increase the effectiveness of tumor radiotherapy. Here we synthesized and investigated MRI active gadolinium-doped lutetium fluoride nanoparticles (LuGdF 3 NPs) with pronounced radiocatalytic activity. The LuGdF 3 NPs were synthesized by the hydrothermal method and characterized by TEM, SEM, EDS, DLS, ELS and UV–visible spectroscopy. A comprehensive cytotoxicity analysis of LuGdF 3 NPs (0.1–1 mM/39–390 μg/mL) was performed on 9 cultures of normal and tumor cells, which revealed a selective cytotoxic effect against murine melanoma (B16/F10), human adenocarcinoma (MCF-7) and human osteosarcoma (MNNG/Hos) cancer cells in concentrations of above 0.5 mM (195 μg/mL). It has been shown that LuGdF 3 NPs effectively accumulate in cancer cells, leading to a decrease in their metabolic activity and inducing cell death via apoptosis. Analysis of the radiosensitizing effect of LuGdF 3 NPs under X-ray irradiation confirmed their effectiveness in 2D cell monolayer and 3D (cell spheroid) experimental models. In the case of monolayer, a remarkable inhibition of the clonogenic activity of cancer cells and a significant increase in apoptotic cells 72 h after irradiation were detected. The identified sensitizing effect for EMT6/P cells was synergistic (CDI = 0.65). It has been shown that LuGdF 3 NPs is capable of disrupting the structure of 3D tumor spheroids under irradiation, inhibiting their growth, significantly reducing the clonogenic (CDI = 0.23) and invasive activity of irradiated cancer cells. Unique relaxivity values of LuGdF 3 NPs for both T1 and T2 were demonstrated, confirming the dual properties of their MRI contrast ability. Effective MRI visualization of the tumor node using T1 and T2 images was confirmed in an in vivo model after intratumoral administration of LuGdF 3 NPs. Thus, LuGdF 3 NPs can be considered as a promising theranostic agent combining unique T1/T2MRI contrast activity and enhanced radiosensitizing effect.