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Maxime Durand,1 Alicia Chateau,1,* Justine Jubréaux,1,* Jérôme Devy,2 Héna Paquot,1 Gautier Laurent,3 Rana Bazzi,3 Stéphane Roux,3 Nicolas Richet,4 Aurélie Reinhard-Ruch,1 Pascal Chastagner,1,5 Sophie Pinel1 1Université de Lorraine, CNRS, CRAN, Nancy, F-54000, France; 2Université de Reims-Champagne-Ardennes, UMR CNRS/URCA 7369, MEDyC, Reims, F-51100, France; 3Université Bourgogne Franche-Comté, UMR 6213 CNRS-UBFC, UTINAM, Besançon, F-25000, France; 4Université de Reims-Champagne-Ardennes, Plateau Technique Mobile de Cytométrie Environnementale MOBICYTE Mobicyte, Reims, F-51100, France; 5CHRU de Nancy, Hôpital d’enfants - Brabois, Vandoeuvre-lès-Nancy, F-54500, France*These authors contributed equally to this workCorrespondence: Sophie Pinel, Email sophie.pinel@univ-lorraine.frPurpose: This study aimed to evaluate the radiosensitizing potential of Au@DTDTPA(Gd) nanoparticles when combined with conventional external X-ray irradiation (RT) to treat GBM.Methods: Complementary biological models based on U87 spheroids including conventional 3D invasion assay, organotypic brain slice cultures, chronic cranial window model were implemented to investigate the impact of RT treatments (10 Gy single dose; 5× 2 Gy or 2× 5 Gy) combined with Au@DTDTPA(Gd) nanoparticles on tumor progression. The main tumor mass and its infiltrative area were analyzed. This work focused on the invading cancer cells after irradiation and their viability, aggressiveness, and recurrence potential were assessed using mitotic catastrophe quantification, MMP secretion analysis and neurosphere assays, respectively.Results: In vitro clonogenic assays showed that Au@DTDTPA(Gd) nanoparticles exerted a radiosensitizing effect on U87 cells, and in vivo experiments suggested a benefit of the combined treatment “RT 2× 5 Gy + Au@DTDTPA(Gd)” compared to RT alone. Invasion assays revealed that invasion distance tended to increase after irradiation alone, while the combined treatments were able to significantly reduce tumor invasion. Monitoring of U87-GFP tumor progression using organotypic cultures or intracerebral grafts confirmed the anti-invasive effect of Au@DTDTPA(Gd) on irradiated spheroids. Most importantly, the combination of Au@DTDTPA(Gd) with irradiation drastically reduced the number, the viability and the aggressiveness of tumor cells able to escape from U87 spheroids. Notably, the combined treatments significantly reduced the proportion of escaped cells with stem-like features that could cause recurrence.Conclusion: Combining Au@DTDTPA(Gd) nanoparticles and X-ray radiotherapy appears as an attractive therapeutic strategy to decrease number, viability and aggressiveness of tumor cells that escape and can invade the surrounding brain parenchyma. Hence, Au@DTDTPA(Gd)-enhanced radiotherapy opens up interesting perspectives for glioblastoma treatment.Graphical Abstract: Keywords: gold nanoparticles, radiotherapy, brain tumor, cancer cell invasion, tumor recurrence

The materials on nanosized dimension exhibit properties that can be significantly different from their massive counterpart, for this reason the increasing investigation developed in this domain continues advancing. Tb3+ and Eu3+ doped Y2O3 in the nanoscale size were obtained by the polyol mediated synthesis. This work presents a general view of nanoparticle synthesis and the aggregation of the same, in order to form nanostructured materials with luminescent properties. Nanometric and nanostructured materials were evaluated by luminescence spectroscopy where the emission spectra observations for the two materials show high similarity. These observations confirm on the one hand that Tb3+ and Eu3+ ions are located in the Y2O3 matrix, on the other hand that the aggregate material are constituted by nanoparticles with resembling size (5 nm).Los materiales a escala nanométrica presentan en general propiedades diferentes a las que presentan las mismas composiciones en estado masivo, motivo por el cual, se incrementa cada día el interés por su estudio fundamental y sus aplicaciones en sistemas de nueva tecnología. Utilizando el método poliol se obtuvieron materiales nanométricos de Y2O3 dopado con Tb3+ y Eu3+. Este documento presenta un panorama general de la síntesis de las nanopartículas y la agregación de las mismas para formar nanoestructuras con propiedades luminiscentes. Los dos tipos de nanomateriales fueron evaluados por espectroscopia de luminiscencia y las observaciones de sus espectros de emisión muestran una gran similitud entre ellos, con lo cual se confirma por un lado que los iones de Tb y Eu se han integrado en la matriz de Y2O3 y por otro lado, que el material agregado está constituido de nanopartículas con un tamaño semejante (5 nm).

By systematically studying the evolution of the optical properties with the content of some doping elements (Eu and Tb) in cubic gadolinium oxide, we demonstrated that the luminescence quenching could be almost entirely suppressed by elaboration of the samples in the nanometer range. Indeed, even if the proportion of quenchers (here surface hydroxyl groups) does increase at this scale, each rare-earth cation possesses an electronic configuration that depends on its distance from the surface and then slightly differs from that of the surrounding atoms. This difference almost eliminates any resonant transfer of excitation between all the atoms within the particle and suppresses a significant proportion of non-radiative losses. As a consequence, the quantum yield is not affected by the phenomenon of luminescence quenching because of concentration that is usually encountered in macroscopic samples. The emission can then be increased by a factor of about 3 for Tb and 5 for Eu simply by increasing the doping content. Moreover, the lifetime is significantly increased compared to macroscopic samples and, contrary to what happens at the macroscopic scale, does not depend on the doping content. This result opens new strategies to increase the emission of many fluorophores already commercialized, provided that the bcc structure is effectively preserved in the desired application. [ABSTRACT FROM AUTHOR]

Terbium doped Y2O3 planar waveguides were fabricated by sol–gel process and dip-coating using yttrium acetate as precursor. Two different doping modes were compared, i.e. introduction in the sol of dispersed Tb3+ions from dissolved Tb(NO3)3, or of nanoparticles of Tb2O3 or [Y2O3:50% Tb] from an alcoholic suspension. The chemical and nanostructural properties were analyzed by infrared spectroscopy, transmission electron microscopy and X-ray diffraction. The Tb3+ fluorescence properties were studied as a function of temperature and atmosphere of the thermal treatments, and of the Tb3+ concentration. The fluorescence properties are discussed in relation to the quenching mechanisms induced by Tb4+ transformation, residual OH groups, and crystallites size and structure. Optical propagation losses of the Tb doped Y2O3 planar waveguides related to the doping modes and Tb3+ concentration are presented. Doping sol–gel films by nanoparticles is shown to be a valuable alternative to the conventional doping from dissolved terbium salt. [ABSTRACT FROM AUTHOR]

Red-emitting Eu3+-doped Gd2O3 spherical powders were directly precipitated using a polyol method. The as-synthesized powders consist of agglomerates with a spherical shape and a size ranging between 0.4 and 0.6 μm. Each agglomerate is nanostructured and consists of a packing of nanocrystallites (3–5 nm) of a bcc oxide phase whose luminescence presents original features in comparison with bulk materials. The powders were further calcinated and the size of both crystallites and agglomerates, the crystalline structure and the luminescence were studied as a function of the annealing temperature. For temperatures lower than 900 °C, the samples obtained are highly crystalline and possess the classical Eu3+ red luminescence. For optimized temperature, the morphology of the particles can be preserved leading to spherical, dense, luminescent and almost monodisperse oxide powders, 0.5 μm in size. [ABSTRACT FROM AUTHOR]

Nanocrystals of oxides containing europium as the main constituent or as a doping element in RE2O3 (RE=Y, Gd) have been prepared by direct oxide precipitation in high-boiling polyalcohol solutions and characterized by high-resolution TEM, absorption spectroscopy, and luminescence spectroscopy. The samples obtained consisted of concentrated and colloidally stable suspensions of luminescent oxide nanoparticles with an average grain diameter in the range 2–5 nm. The nanoparticles were found to be highly crystalline despite their ultrasmall size and the low temperature of 180 °C applied during the synthesis. Upon UV excitation, the red luminescence relative to the 5D0→7Fn transition within the cubic form of RE2O3 exhibits some important differences from that usually found in bulk materials. [Copyright &y& Elsevier]

The characterization and luminescence properties of nanostructured Gd2O3:Eu3+ phosphors synthesized by a sol-lyophilization process are presented. After preparation of gadolinium-based sols from gadolinium nitrate and ammonium hydroxide, the so-prepared sols were freeze dried at −10°C and calcinated at different temperatures. For temperatures lower than 1300 K, highly crystalline samples with the cubic structure can be obtained without concomitant grain growth of the particles (<50 nm). The luminescence spectra contain all possible transitions of Eu3+ with C2 symmetry and present two major features: an increase of the luminescence efficiencies of the phosphors in comparison with that obtained by solid-state reaction and the presence of an additional peak at about 609 nm at the vicinity of the 5D0→7F0…4 transition. [Copyright &y& Elsevier]

Abstract: Nano-structured powders and fiber single crystals of cubic yttrium oxide undoped and Eu2O3 doped with luminescent properties were prepared using two techniques. The first one is focused on direct oxide precipitation at low temperature in which europium-doped yttrium oxide (Y2O3:Eu3+) particles sizes less than 5nm were synthesized in colloidal solution, followed by a controlled precipitation to obtain fine sub-micrometric powders. The second method is based on fiber single crystal growth using laser-heated pedestal growth (LHPG) and CO2 laser beam as heating source at 10.6μm and homogeneous starting rod materials obtained from the synthesis of nano-scale materials. The fibers grown by LHPG technique were single crystal, transparent, homogeneous, red color when Eu3+ concentration is high. The crystal fiber quality decreases with increasing Eu3+ concentration higher than 2% because of segregation problem. The materials obtained by the soft chemistry are cubic and lies in the nano-meter range. The purity of the materials, europium concentration limit, particles sizes and structure were obtained from X-ray powders diffraction at room temperature. The segregation coefficient of Eu3+ is measured from EPMA analysis. The morphology of the materials was obtained using SEM. The luminescence of Eu3+ has been detected by excitation at . [Copyright &y& Elsevier]

Gd2−xEuxO3 powder materials doped with Eu3+ using different concentration from x=0 to 2 were prepared by a new sol-lyophilization synthesis and fiber single crystal (Gd2O3–Gd2O3/Eu3+) oxides were grown using laser-heated pedestal growth (LHPG) technique. X-ray powder diffraction performed at room temperature showed that the materials obtained by lyophilization technique are cubic, lies in the nanometer range and different from bulk materials. The materials are a continued solid solution and the lattice parameter a-axis increases with Eu3+ concentration. The fibers grown by LHPG technique were single crystal, transparent, red in color when Eu3+ concentration is high, and the structure is monoclinic for Eu3+<15%. The luminescence of Eu3+ from C2 crystallographic site was been detected. In the case of nano-particles oxide, an additional peak in emission spectral is obtained at λ=610 nm. The influence of Eu3+, particles sizes and the structure on the luminescence spectral of Eu3+ ions was been described. [Copyright &y& Elsevier]

We elucidate the decomposition mechanism of hydrogen peroxide, which is formed by water radiolysis, by gold nanoparticles (GNPs) under X-ray irradiation. The variations in yields of hydrogen peroxide generated in the presence of GNPs are evaluated using the Ghormley technique. The increase of yields of OH radicals has been quantified using Ampliflu® Red solutions. Almost all hydrogen peroxide generated by irradiation of <25 Gy is decomposed by GNPs, while the yield of OH radicals increases by 1.6 times. The amount of OH radicals thus obtained is almost equivalent to that of the decomposed hydrogen peroxide. The decomposition of hydrogen peroxide is an essential reaction to produce additional OH radicals efficiently in the vicinity of GNPs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: Traumatic brain injury (TBI) is the largest cause of death from injury in the United States. This study utilized the Michigan Trauma Quality Improvement Program (MTQIP) database to determine the effect that antiplatelets and anticoagulants (AP/AC) have on outcomes following emergent surgery for TBI patients., Basic Procedures: Patients were included with age ≥18 years, maximum head/neck abbreviated injury score (AIS) ≥2, and underwent a neurosurgical procedure within 24 hours. Patients were excluded if they had an AIS ≥3 in other body region or no signs of life at initial evaluation., Main Findings: Within the 1,932 patients analyzed, 139 (8.74%) were in the warfarin with or without (+/-) aspirin cohort, 101 (6.35%) in the direct oral anticoagulants (DOAC) +/- aspirin cohort, 169 (10.62%) in the clopidogrel +/- aspirin cohort, and 1,182 (74.29%) in the no AP/AC cohort (control group). After controlling for demographic and clinical characteristics, no significant difference in mortality rates was observed in the treatment groups ( P > 0.05). However, our subgroup analysis did reveal a significantly higher mortality rate within the warfarin and aspirin subgroup when compared to the control group (odds ratio [OR], 2.368; confidence interval [CI], 1.306-4.294, P = 0.005). With regards to hospital complications, there was a significant increase in this outcome within the DOAC +/- aspirin (OR, 1.825; CI, 1.143-2.915, P = 0.012) and clopidogrel +/- aspirin (OR, 1.82; CI, 1.244-2.663, P =0.002) groups., Conclusion: Patients on AP/AC who experience a TBI requiring an emergent operation do not have an increased risk of mortality compared to patients not on AP/AC., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Biomedical photothermal therapy with optical nanoparticles is based on the conversion of optical energy into heat through three steps: optical absorption, thermal conversion of the absorbed energy and heat transfer to the surrounding medium. The light-to-heat conversion efficiency (LHCE) has become one of the main metrics to quantitatively characterize the last two steps and evaluate the merit of nanoparticules for photothermal therapy. The estimation of the LHCE is mostly performed by monitoring the temperature evolution of a solution under laser irradiation. However, this estimation strongly depends on the experimental set-up and the heat balance model used. We demonstrate here, theoretically and experimentally, that the LHCE at multiple wavelengths can be efficiently and directly determined, without the use of models, by calibrated photoacoustic spectroscopy. The method was validated using already characterized colloidal suspensions of silver sulfide nanoparticles and maghemite nanoflowers and an uncertainty of 3 to 7% was estimated for the LHCE determination. Photoacoustic spectroscopy provides a new, precise and robust method of analysis of the photothermal capabilities of aqueous solutions of nanoagents.

Introduction: Trauma outcomes can be greatly affected by antiplatelet and anticoagulant (AP/AC) use. The goal of this study was to compare outcomes in trauma patients on AP/AC undergoing emergent surgery for thoracoabdominal trauma at 35 level 1 and 2 trauma centers from 2014 to 2021., Methods: This was a retrospective cohort study of 2460 adult patients with a chest, abdomen, or pelvis abbreviated injury score (AIS) of 2 or more who underwent surgery within 24 h of admission. These patients were segregated into four main cohorts based on antiplatelet/anticoagulation use: those not on AP/AC, those taking direct-acting oral anticoagulants (DOACs), those taking clopidogrel, and those taking warfarin. Patients were excluded if they had surgery >24 h after presentation, were dead on arrival, or had any other body system AIS score of 3 or higher., Results: The mean injury severity score (ISS) in all four groups ranged from 16.3 to 18.6 ( p  = 0.834) with a mean time to operating room from 208 to 478 min ( p  < 0.001). Laparotomy was performed in 60 to 71 % ( p  > 0.01) of patients, regardless of AP/AC status, and thoracic procedures were performed in 3.1 to 9.3 % ( p  = 0.42) of patients. In-hospital mortality and hospice rates were highest in the clopidogrel group at 21.9 %, followed by warfarin at 13 %, DOACs at 15 %, and no AP/AC at 7.63 % ( p  = 0.008). Serious complications occurred in 61 % of patients on warfarin, 50 % of those on DOACs, and 44 % of those on clopidogrel. All of these groups demonstrated significantly higher complication rates than patients in the no AP/AC control group at 25 % ( p  < 0.001). Total transfusion of packed red blood cells and fresh frozen plasma did not differ significantly between the groups; however, 24-h platelet transfusion did. Patients on clopidogrel received 14 packs of platelets, while those on warfarin and DOACs received 8 and 13 packs respectively ( p  = 0.011). Patients on warfarin had the longest hospital length of stay (LOS) at 13 days and ICU LOS at 9 days, compared to those on DOACs (8 and 4), those on clopidogrel (7 and 3), and those not taking AC/AP (7 and 4) (hospital LOS p  = 0.03, ICU LOS p  = 0.019). Those on AC/AP were also noted to be significantly older than those on neither, with those taking these medications averaging out to be approximately 69 years old and those not on these medications averaging 37 years old ( p  < 0.001)., Conclusion: There was significantly higher mortality in patients on clopidogrel and increased length of stay and risk of serious complications in patients taking DOACs and warfarin. In patients on AP/AC there was also a significantly longer time to surgery than in those not taking either. Given these associations trauma surgeons should consider intervening sooner on patients taking AP/AC on admission, as the delay to intervention may contribute to the risks for trauma patients and result in worse outcomes as well as higher rates of mortality., Competing Interests: The authors have no conflict of interest to disclose., (© 2023 The Authors.)

Glioblastoma (GBM) is known as the most aggressive type of malignant brain tumour, with an extremely poor prognosis of approximately 12 months following standard-of-care treatment with surgical resection, radiotherapy (RT), and temozolomide treatment. Novel RT-drug combinations are urgently needed to improve patient outcomes. Gold nanoparticles (GNPs) have demonstrated significant preclinical potential as radiosensitizers due to their unique physicochemical properties and their ability to pass the blood-brain barrier. The modification of GNP surface coatings with poly(ethylene) glycol (PEG) confers several therapeutic advantages including immune avoidance and improved cellular localisation. This study aimed to characterise both the radiosensitizing and immunomodulatory properties of differentially PEGylated GNPs in GBM cells in vitro. Two GBM cell lines were used, U-87 MG and U-251 MG. The radiobiological response was evaluated by clonogenic assay, immunofluorescent staining of 53BP1 foci, and flow cytometry. Changes in the cytokine expression levels were quantified by cytokine arrays. PEGylation improved the radiobiological efficacy, with double-strand break induction being identified as an underlying mechanism. PEGylated GNPs also caused the greatest boost in RT immunogenicity, with radiosensitization correlating with a greater upregulation of inflammatory cytokines. These findings demonstrate the radiosensitizing and immunostimulatory potential of ID11 and ID12 as candidates for RT-drug combination in future GBM preclinical investigations.

Functional colloidal nanoparticles capable of converting between various energy types are finding an increasing number of applications. One of the relevant examples concerns light-to-heat-converting colloidal nanoparticles that may be useful for localized photothermal therapy of cancers. Unfortunately, quantitative comparison and ranking of nanoheaters are not straightforward as materials of different compositions and structures have different photophysical and chemical properties and may interact differently with the biological environment. In terms of photophysical properties, the most relevant information to rank these nanoheaters is the light-to-heat conversion efficiency, which, along with information on the absorption capacity of the material, can be used to directly compare materials. In this work, we evaluate the light-to-heat conversion properties of 17 different nanoheaters belonging to different groups (plasmonic, semiconductor, lanthanide-doped nanocrystals, carbon nanocrystals, and metal oxides). We conclude that the light-to-heat conversion efficiency alone is not meaningful enough as many materials have similar conversion efficiencies─in the range of 80-99%─while they significantly differ in their extinction coefficient. We therefore constructed their qualitative ranking based on the external conversion efficiency, which takes into account the conventionally defined light-to-heat conversion efficiency and its absorption capacity. This ranking demonstrated the differences between the samples more meaningfully. Among the studied systems, the top-ranking materials were black porous silicon and CuS nanocrystals. These results allow us to select the most favorable materials for photo-based theranostics and set a new standard in the characterization of nanoheaters.