Particle Size of X-ray Pumped UVC-Emitting Nanoparticles Defines Intracellular Localization and Biological Activity Against Cancer Cells

Effectiveness of radiation treatment for cancer is limited in hypoxic tumors. Previous data shows that UVC-emitting nanoparticles enhance cytotoxicity of X-ray irradiation in hypoxic tumor cells. This study examines the impact on cell killing, particle size, uptake into cells, incubation time, and UV emission intensity of LuPO₄:Pr³⁺,Nd³⁺. A549 cells are treated with LuPO₄:Pr³⁺,Nd³⁺ and X-rays. The surviving fraction is evaluated using the colony formation assay after treatment of cells with different particle sizes (D₅₀ = 0.16 and 5.05 µm) and after different incubation times before X-ray irradiation. Nanoparticle uptake into cells is verified by transmission electron microscopy and quantified by inductively coupled plasma mass spectrometry. The microparticles exhibit a five times higher emission intensity compared to nanoparticles. Both particle sizes show an increased cytotoxic effect after X-ray excitation with prolonged incubation times. Surprisingly, the smaller nanoparticles show a significantly higher biological effect compared to the larger particles, despite their significantly lower UVC emission. Nanoparticles accumulate more quickly and closer to the nucleus than the microparticles, resulting in higher localized UVC emission and greater lethality. The results suggest that the number of intracellular particles and their proximity to the cell DNA is more important than the emission intensity of the particles.