First in vitro cell co-culture experiments using laser-induced high-energy electron FLASH irradiation for the development of anti-cancer therapeutic strategies.

Radiation delivery at ultrahigh dose rates (UHDRs) has potential for use as a new anticancer therapeutic strategy. The FLASH effect induced by UHDR irradiation has been shown to maintain antitumour efficacy with a reduction in normal tissue toxicity; however, the FLASH effect has been difficult to demonstrate in vitro. The objective to demonstrate the FLASH effect in vitro is challenging, aiming to reveal a differential response between cancer and normal cells to further identify cell molecular mechanisms. New high-intensity petawatt laser-driven accelerators can deliver very high-energy electrons (VHEEs) at dose rates as high as 1013 Gy/s in very short pulses (10-13 s). Here, we present the first in vitro experiments carried out on cancer cells and normal non-transformed cells concurrently exposed to laser-plasma accelerated (LPA) electrons. Specifically, melanoma cancer cells and normal melanocyte co-cultures grown on chamber slides were simultaneously irradiated with LPA electrons. A non-uniform dose distribution on the cell cultures was revealed by Gafchromic films placed behind the chamber slide supporting the cells. In parallel experiments, cell co-cultures were exposed to pulsed X-ray irradiation, which served as positive controls for radiation-induced nuclear DNA double-strand breaks. By measuring the impact on discrete areas of the cell monolayers, the greatest proportion of the damaged DNA-containing nuclei was attained by the LPA electrons at a cumulative dose one order of magnitude lower than the dose obtained by pulsed X-ray irradiation. Interestingly, in certain discrete areas, we observed that LPA electron exposure had a different effect on the DNA damage in healthy normal human epidermal melanocyte (NHEM) cells than in A375 melanoma cells; here, the normal cells were less affected by the LPA exposure than cancer cells. This result is the first in vitro demonstration of a differential response of tumour and normal cells exposed to FLASH irradiation and may contribute to the development of new cell culture strategies to explore fundamental understanding of FLASH-induced cell effect.

Y2O3 Nanoparticles and X-ray Radiation-Induced Effects in Melanoma Cells.

The innovative strategy of using nanoparticles in radiotherapy has become an exciting topic due to the possibility of simultaneously improving local efficiency of radiation in tumors and real-time monitoring of the delivered doses. Yttrium oxide (Y2O3) nanoparticles (NPs) are used in material science to prepare phosphors for various applications including X-ray induced photodynamic therapy and in situ nano-dosimetry, but few available reports only addressed the effect induced in cells by combined exposure to different doses of superficial X-ray radiation and nanoparticles. Herein, we analyzed changes induced in melanoma cells by exposure to different doses of X-ray radiation and various concentrations of Y2O3 NPs. By evaluation of cell mitochondrial activity and production of intracellular reactive oxygen species (ROS), we estimated that 2, 4, and 6 Gy X-ray radiation doses are visibly altering the cells by inducing ROS production with increasing the dose while at 6 Gy the mitochondrial activity is also affected. Separately, high-concentrated solutions of 25, 50, and 100 µg/mL Y2O3 NPs were also found to affect the cells by inducing ROS production with the increase of concentration. Additionally, the colony-forming units assay evidenced a rather synergic effect of NPs and radiation. By adding the NPs to cells before irradiation, a decrease of the number of proliferating cell colonies was observed with increase of X-ray dose. DNA damage was evidenced by quantifying the γ-H2AX foci for cells treated with Y2O3 NPs and exposed to superficial X-ray radiation. Proteomic profile confirmed that a combined effect of 50 µg/mL Y2O3 NPs and 6 Gy X-ray dose induced mitochondria alterations and DNA changes in melanoma cells.

Structural, Compositional, and Mechanical Characterization of WxCryFe1-x-y Layers Relevant to Nuclear Fusion, Obtained with TVA Technology.

Reduced activation ferritic and martensitic steel like EUROFER (9Cr-1W) are considered as potential structural materials for the first wall of the future next-generation DEMOnstration Power Station (DEMO) fusion reactor and as a reference material for the International Thermonuclear Experimental Reactor (ITER) test blanket module. The primary motivation of this work is to study the re-deposition of the main constituent materials of EUROFER, namely tungsten (W), iron (Fe), and chromium (Cr), in a DEMO type reactor by producing and analyzing complex WxCryFe1-x-y layers. The composite layers were produced in laboratory using the thermionic vacuum arc (TVA) method, and the morphology, crystalline structure, elemental composition, and mechanical properties were studied using scanning electron microscopy (SEM), X-ray diffraction (XRD), micro-X-ray fluorescence (micro-XRF), and glow discharge optical emission spectrometry (GDOES), as well as nanoindentation and tribology measurements. The results show that the layer morphology is textured and is highly dependent on sample positioning during the deposition process. The formation of polycrystalline WxCryFe1-x-y was observed for all samples with the exception of the sample positioned closer to Fe anode during deposition. The crystalline grain size dimension varied between 10 and 20 nm. The composition and thickness of the layers were strongly influenced by the in-situ coating position, and the elemental depth profiles show a non-uniform distribution of Fe and Cr in the layers. The highest hardness was measured for the sample positioned near the Cr anode, 6.84 GPa, and the lowest was 4.84 GPa, measured for the sample positioned near the W anode. The tribology measurements showed an abrasive sliding wear behavior for most of the samples with a reduction of the friction coefficient with the increase of the normal load.

Near infrared emission properties of Er doped cubic sesquioxides in the second/third biological windows.

In the recent years, there is an extensive effort concentrated towards the development of nanoparticles with near-infrared emission within the so called second or third biological windows induced by excitation outside 800-1000 nm range corresponding to the traditional Nd (800 nm) and Yb (980 nm) sensitizers. Here, we present a first report on the near-infrared (900-1700 nm) emission of significant member of cubic sesquioxides, Er-Lu2O3 nanoparticles, measured under both near-infrared up-conversion and low energy X-ray excitations. The nanoparticle compositions are optimized by varying Er concentration and Li addition. It is found that, under ca. 1500 nm up-conversion excitation, the emission is almost monochromatic (>93%) and centered at 980 nm while over 80% of the X-ray induced emission is concentrated around 1500 nm. The mechanisms responsible for the up-conversion emission of Er - Lu2O3 are identified by help of the up-conversion emission and excitation spectra as well as emission decays considering multiple excitation/emission transitions across visible to near-infrared ranges. Comparison between the emission properties of Er-Lu2O3 and Er-Y2O3 induced by optical and X-ray excitation is also presented. Our results suggest that the further optimized Er-doped cubic sesquioxides represent promising candidates for bioimaging and photovoltaic applications.

Defect induced tunable near infrared emission of Er-CeO2 by heterovalent co-dopants.

We investigate the effects of heterovalent co-dopants on the structural and emission properties of 1% Er-CeO2 nanoparticles. The CeO2 oxide host was selected on the basis of its fairly well-understood defect chemistry in either a pure or doped state. As a luminescent activator, Er is acknowledged as an interesting element due to its rich luminescence and excitation properties spanning the visible to near-infrared range. The optically inactive trivalent La and monovalent Li metal ions with a concentration of up to 20% were chosen to presumably generate a variable amount of defects in the Er-CeO2 lattice. It was found that La and Li co-dopants induced distinct changes related to the size, lattice constant, bandgap energy, lattice and surface defects of Er-CeO2. As a result of these changes, a strong modulation of the luminescence intensity and shape was measured using a suite of excitation conditions (charge-transfer absorption band of CeO2, direct/up-conversion into Er absorptions and X-ray excitation modes). The use of Eu as a luminescent probe offered additional information concerning the effects of La/Li co-doping on the local structure surrounding the luminescent activator. Remarkably high percentages of 90 and 98% of the total emission of Er measured between 500 and 1100 nm are measured in the near-infrared region at 980 nm under X-ray and up-conversion excitation at ∼1500 nm, respectively. The optical properties suggest that Li, Er co-doped CeO2 has good potential for therapy and biological imaging.

Evaluation of reconstruction errors and identification of artefacts for JET gamma and neutron tomography.

The Joint European Torus (JET) neutron profile monitor ensures 2D coverage of the gamma and neutron emissive region that enables tomographic reconstruction. Due to the availability of only two projection angles and to the coarse sampling, tomographic inversion is a limited data set problem. Several techniques have been developed for tomographic reconstruction of the 2-D gamma and neutron emissivity on JET, but the problem of evaluating the errors associated with the reconstructed emissivity profile is still open. The reconstruction technique based on the maximum likelihood principle, that proved already to be a powerful tool for JET tomography, has been used to develop a method for the numerical evaluation of the statistical properties of the uncertainties in gamma and neutron emissivity reconstructions. The image covariance calculation takes into account the additional techniques introduced in the reconstruction process for tackling with the limited data set (projection resampling, smoothness regularization depending on magnetic field). The method has been validated by numerically simulations and applied to JET data. Different sources of artefacts that may significantly influence the quality of reconstructions and the accuracy of variance calculation have been identified.

Pure and almost pure NIR emission of Tm and Tm,Yb-CeO2 under UV, X-ray and NIR up-conversion excitation: key roles of level selective antenna sensitization and charge-compensation.

Herein, we report on the pure and almost pure near-infrared (NIR) emission at around 807 nm observed for Tm(Yb) (co)-doped CeO2 nanoparticles (NPs) under UV, X-ray and NIR up-conversion excitation. The optical responses are attributed to the low-lying charge-transfer of CeO2 that acts as a selective antenna sensitizer of the Tm (3)H4 emission and Yb doping that lowers the local symmetry at Tm sites and introduces additional phonon modes. Selective antenna sensitization is also observed for Er/Ho (Yb) (co)-doped CeO2 NPs. To the best of our knowledge, this is a first study which correlates the down- and up-conversion emission properties of lanthanide(s)-(co) dopants with the CeO2 structure highlighting also the outstanding potential of these NPs in high-penetration tissue imaging and therapy.