Thulium Oxide Nanoparticles: A new candidate for image-guided radiotherapy

Abstract

Nanoparticles, with their distinct properties that vary from their bulk material equivalent, continue to gain popularity for studies into multi-modal applications in medicine. This research introduces the use of thulium oxide nanoparticles for biological applications and characterizes the potential of this novel nanoparticle for image-guided radiotherapy of brain cancer. In this study, we investigate the structural characteristics of this nanoparticle, and reveal a significant dose enhancement towards radioresistant brain tumour cells in vitro that also underlies an improvement in the CT image contrast of brain tumours in vivo. The thulium oxide nanoparticles utilized in the investigations described in this article were measured to be 40-45 nm from x-ray diffraction and scanning electron microscopy data. In vitro investigations assessed the cell survival and DNA damage in 9 l gliosarcoma cells following irradiation with 150 kVp orthovoltage x-rays. Immediately after the 150 kVp irradiation (15 min) an increase in the number of γ-H2AX induced foci indicates the production of more double-strand DNA breaks. Following from the short time-frame irradiation outcomes, clonogenic cell survival assays confirmed long-term radio-sensitization, with the cell sensitivity increasing by a factor of 1.32 (measured at the 10% survival fraction) for the irradiated 9 l cells exposed to thulium nanoparticles. A simple CT experiment shows that our thulium nanoparticles suspended in water at concentrations >0.5 mg ml −1 (0.05-20 mg ml −1 investigated) are clearly observable against water. Extending the CT experiment to an in vivo investigation, cellular uptake of the nanoparticles was demonstrated through CT image enhancement of the cancer site in 9-to 10-week-old Fisher rats bearing 9 l gliosarcomas, 12 days after cell implantation. The 9 l cancer is clearly visible on the CT image after injecting 40 μg of nanoparticles (2 μl at 20 mg ml −1) directly to the cancer site (5.5 mm from the dura and 3.5 mm right laterally of the bregma, 5 mm depth). To our knowledge, this work demonstrates the first application of thulium nanoparticles in biology and medicine, for radiotherapy and image guidance purposes.

Toward personalized synchrotron microbeam radiation therapy

“…The response of 9LGS towards specific treatments such as MRT or broad beam in our study offered a means of clarifying certain trends in tumor sensitivity to radiation directly before in vivo treatment. Conventional www.nature.com/scientificreports www.nature.com/scientificreports/ kilovoltage radiotherapy of 9LGS (shown previously 47 ), identified the significant radioresistance of cells at clinical dose rates (in order of <1 Gy/min). Synchrotron radiation was superior to conventional X-rays in the treatment of 9LGS if delivered at a dose rate of 205 Gy/s.…”

Iodine nanoparticles enhance radiotherapy of intracerebral human glioma in mice and increase efficacy of chemotherapy

“…Materials with elements that highly absorb X-rays are potent radioenhancers, but their effective clinical translation has been virtually non-existent. AuNPs have been extensively studied for over 14 years 3 (recent review 5 ) and other nanoparticles containing gadolinium 53 , bismuth 54 , titanium 55 , thulium 56 , platinum 57 , and hafnium 58 have also been investigated. Iodine contrast media were used in clinical trials first by Norman and coworkers 12 , then later by Adam and coworkers 14 .…”

The Rational Design and Biological Mechanisms of Nanoradiosensitizers

“…Metal oxide NPs exhibited radiosensitization effects through DNA damage or the inhibition of DNA repair. Thulium oxide NPs (40-45 nm) enhanced DSBs in radioresistant 9L brain gliosarcoma cells under irradiation [98]. The combined chemoradiotherapy of DOX-loaded mesoporous tantalum oxide (mTa 2 O 5 , 80 nm) NPs led to a strong synergistic therapeutic effect in a mouse tumor model.…”