severe side effects. [2,3] Complicated irradiation plans are usually used to ensure irradiation of only the tumor and to avoid irradiation of surrounding healthy tissue. Furthermore, some tumors contain hypoxic cells that are resistant to cell killing by ionizing radiation and require higher doses or other approaches to eliminate them. Molecules or particles that can accumulate in tumors and act as radiation scintillators to enhance local tumor sensitivity to X-ray irradiation are of great interest for a more selective and effective cancer treatment. Recently, UVC-emitting LuPO 4 :Pr 3+ nanoparticles were shown to increase the local radiation dose resulting in increased cell death under normoxic as well as under hypoxic conditions. [4,5] The high atomic number of lutetium (Z = 71) ensures an efficient absorption of X-rays while the dopant praseodymium (Pr 3+) is responsible for the emission of UVC photons after X-ray excitation to directly damage the DNA of the cells in an oxygen independent mechanism. Similar to gold nanoparticles, the high atomic number leads to a higher absorption cross section and thus generates a higher radiation absorption contrast between the tumor and healthy tissue when the nanoparticles are localized to a tumor. There is also an increasing interest to use scintillating materials made of elements with high 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 LuPO 4 :Pr 3+ ,Nd 3+. A549 cells are treated with LuPO 4 :Pr 3+ ,Nd 3+ and X-rays. The surviving fraction is evaluated using the colony formation assay after treatment of cells with different particle sizes (D 50 = 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.