A comparison of the radiosensitisation ability of 22 different element metal oxide nanoparticles using clinical megavoltage X-rays

Background: A wide range of nanoparticles (NPs), composed of different elements and their compounds, are being developed by several groups as possible radiosensitisers, with some already in clinical trials. However, no systematic experimental survey of the clinical X-ray radiosensitising potential of different element nanoparticles has been made. Here, we directly compare the irradiation-induced (10 Gy of 6-MV X-ray photon) production of hydroxyl radicals, superoxide anion radicals and singlet oxygen in aqueous solutions of the following metal oxide nanoparticles: Al2O3, SiO2, Sc2O3, TiO2, V2O5, Cr2O3, MnO2, Fe3O4, CoO, NiO, CuO, ZnO, ZrO2, MoO3, Nd2O3, Sm2O3, Eu2O3, Gd2O3, Tb4O7, Dy2O3, Er2O3 and HfO2. We also examine DNA damage due to these NPs in unirradiated and irradiated conditions. Results: Without any X-rays, several NPs produced more radicals than water alone. Thus, V2O5 NPs produced around 5-times more hydroxyl radicals and superoxide radicals. MnO2 NPs produced around 10-times more superoxide anions and Tb4O7 produced around 3-times more singlet oxygen. Lanthanides produce fewer hydroxyl radicals than water. Following irradiation, V2O5 NPs produced nearly 10-times more hydroxyl radicals than water. Changes in radical concentrations were determined by subtracting unirradiated values from irradiated values. These were then compared with irradiation-induced changes in water only. Irradiation-specific increases in hydroxyl radical were seen with most NPs, but these were only significantly above the values of water for V2O5, while the Lanthanides showed irradiation-specific decreases in hydroxyl radical, compared to water. Only TiO2 showed a trend of irradiation-specific increase in superoxides, while V2O5, MnO2, CoO, CuO, MoO3 and Tb4O7 all demonstrated significant irradiation-specific decreases in superoxide, compared to water. No irradiation-specific increases in singlet oxygen were seen, but V2O5, NiO, CuO, MoO3 and the lanthanides demonstrated irradiation-specific decreases in singlet oxygen, compared to water. MoO3 and CuO produced DNA damage in the absence of radiation, while the highest irradiation-specific DNA damage was observed with CuO. In contrast, MnO2, Fe3O4 and CoO were slightly protective against irradiation-induced DNA damage. Conclusions: Beyond identifying promising metal oxide NP radiosensitisers and radioprotectors, our broad comparisons reveal unexpected differences that suggest the surface chemistry of NP radiosensitisers is an important criterion for their success

Generalists as sequential specialists: Diets and prey switching in juvenile silver perch

Diets of silver perch, Bidyanus bidyanus in organically fertilised aquaculture ponds were dominated by chironomid larvae, Daphnia and calanoid copepods. Insects and crustaceans contributed approximately 80% and 20% by weight to the diet respectively. Classification of the stomach contents of individual fish revealed 8 diet groups, 4 of which were dominated by planktonic crustaceans and 4 by insects. Each diet group was strongly dominated by a different prey type. Fish from the same sample tended to belong to the same diet group and there was a non-random distribution of diet groups across ponds. Perch diets were influenced by the method of pond fertilisation (livestock effluent or pellet feed). Shifts in the representation of groups indicated that fish switched from one diet group to another over a 2-4 week period. The selection of planktonic prey by perch was related to prey densities in the ponds. Fish preferred Daphnia when these prey were common, but switched to calanoids and insects when Daphnia were scarce. A perfect rank correlation between the mean body size of planktonic prey and their contribution to the diet suggested that prey choice involved comparative decisions based on prey size. These findings indicate that, while classified as dietary generalists, silver perch exhibit consumption patterns which at the individual level are highly specialised at any given time. These patterns can be predicted, given information on prey densities in the environment

Monte Carlo simulations guided by imaging to predict the in vitro ranking of radiosensitizing nanoparticles

Paul Retif,1–3 Aurélie Reinhard,2,3 Héna Paquot,2,3 Valérie Jouan-Hureaux,2,3 Alicia Chateau,2,3 Lucie Sancey,4 Muriel Barberi-Heyob,2,3 Sophie Pinel,2,3 Thierry Bastogne2,3,5 1Unité de Physique Médicale, CHR Metz-Thionville, Ars-Laquenexy, 2Université de Lorraine, 3CRAN, UMR 7039, CNRS, Vandoeuvre-lès-Nancy, 4Institut Lumière Matière, UMR 5306, CNRS, Villeurbanne, 5INRIA-BIGS & CRAN, Université de Lorraine, Vandoeuvre-lès-Nancy Cedex, France Abstract: This article addresses the in silico–in vitro prediction issue of organometallic nanoparticles (NPs)-based radiosensitization enhancement. The goal was to carry out computational experiments to quickly identify efficient nanostructures and then to preferentially select the most promising ones for the subsequent in vivo studies. To this aim, this interdisciplinary article introduces a new theoretical Monte Carlo computational ranking method and tests it using 3 different organometallic NPs in terms of size and composition. While the ranking predicted in a classical theoretical scenario did not fit the reference results at all, in contrast, we showed for the first time how our accelerated in silico virtual screening method, based on basic in vitro experimental data (which takes into account the NPs cell biodistribution), was able to predict a relevant ranking in accordance with in vitro clonogenic efficiency. This corroborates the pertinence of such a prior ranking method that could speed up the preclinical development of NPs in radiation therapy. Keywords: biomedical applications of radiations, computer simulation, nanomedicine, virtual screenin

Plateforme MO2VING: from MOlecular Organization to in Vivo ImagiNG

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