UV Emitting Nanoscale Scintillators for Biomedical Applications

In the medical field, the applications of ultraviolet (UV) radiation are limited to skin or reachable sites due to its low penetration depth into biological tissue. Contrary to UV radiation, X-rays can penetrate the body with almost no attenuation, but they result in toxic side effects. Inorganic scintillators absorb X-rays and convert them into UV or visible photons and are usually used for medical imaging. We propose the use of high density inorganic nanoscale scintillators with the ability to absorb externally applied ionizing radiation directly at the site of application, e.g., inside a tumor, and to convert this ionizing radiation into UV photons in situ, enabling new biomedical applications inside the body. In this thesis, two specific new biomedical applications are discussed in detail: The first application is the use of UV-B emitting nanoscale scintillators for highly localized drugs released or activation of photoactivable therapeutics using only X-rays. The second novel approach is the use of UV-C emitting nanoscale scintillators as radiation sensitizers. However, size-reduction of inorganic scintillators, and most inorganic phosphors in general, usually result in quenching of the photoluminescence properties, defects on the surface of the particles, and a decrease of radiation hardness. Colloidal solutions of nearly monodisperse LaPO4:Gd nanocrystals (5nm) were shown to strongly emit UV radiation upon excitation with X-rays or vacuum UV radiation (160nm). The UV emission of the particles consisted mainly of a single line at 311nm. This UV-B emission of the particles was used to excite the fluorescence of laser dyes dissolved in the colloids. The emission of the dyes was also observed in the case of high dye concentrations, proving that the concept of using radiation with a high penetration depth (X-rays) to excite fluorescence emission with a low penetration depth (UV-B) wavelength is feasible. Pr-doped LuPO4 emits UV-C radiation between 225 and 280nm, where DNA shows strong absorption bands. Therefore, a systematic study of the luminescence of LuPO4:Pr was performed: Different doping concentrations, particle sizes, and excitation sources were compared. Furthermore, it was found that Pr and Nd co-doped LuPO4 results in increased UV-C emission independent of excitation source due to energy transfer. The highest UV-C emission intensity was observed for LuPO4:Pr,Nd(1%,2.5%) upon X-ray irradiation. Finally, LuPO4:Pr,Nd nanoparticles were synthesized, and the biological efficacy of the combined approach (X-rays and UV-C) was assessed using the colony formation assay. Cell culture experiments confirm increased cell death compared to X-rays alone due to the formation of UV-specific DNA damages, supporting the application of the herein synthesized particles as radiation sensitizers