2020 |
Le Sech, C., Le Sech C, Hirayama, R., & Hirayama R. (2020). Dual aspect of radioenhancers and free radical scavengers. Free Radic Biol Med, .
Résumé: Combining an external beam of ionizing particles with agents to augment the dose effects of cell damages for therapeutic purpose is an important goal of radiotherapy. This last decade intensive works have focused on metal compounds or metal nanoparticles as radiosensitizers to increase the oxidative damages under irradiation. In principle the nanoparticles can be coated with a functionalized shell, to achieve a specific targeting of the tissues, making such approach attractive. The functionalized coating is made of polymers. These molecules are able to scavenge the free radicals, thus, the coating can decrease the overall efficacy of the radiation. The purpose of the present model is to analyse the role of free hydroxyl radicals in the dual behaviour of the added agent. Consideration of the efficiency of the added agents versus the Linear Energy Transfer – LET – of the ionizing particles is made. It is shown that an efficient agent combined with a low-LET particle beams might become less efficient when high-LET particles like heavy-ions are used. These general considerations should be useful to optimize the design of the nanoparticles to be combined with the different kind of ionizing particles.
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Li X, Porcel, E., Menendez-Miranda, M., Qiu, J., Yang, X., Serre, C., Pastor, A., Desmaele, D., Lacombe S, & Gref, R. (2020). Highly Porous Hybrid Metal-Organic Nanoparticles Loaded with Gemcitabine Monophosphate: a Multimodal Approach to Improve Chemo- and Radiotherapy. (Vol. 15).
Résumé: Nanomedicine recently emerged as a novel strategy to improve the performance of radiotherapy. Herein we report the first application of radioenhancers made of nanoscale metal-organic frameworks (nanoMOFs), loaded with gemcitabine monophosphate (Gem-MP), a radiosensitizing anticancer drug. Iron trimesate nanoMOFs possess a regular porous structure with oxocentered Fe trimers separated by around 5 A (trimesate linkers). This porosity is favorable to diffuse the electrons emitted from nanoMOFs due to activation by gamma radiation, leading to water radiolysis and generation of hydroxyl radicals which create nanoscale damages in cancer cells. Moreover, nanoMOFs act as “Trojan horses”, carrying their Gem-MP cargo inside cancer cells to interfere with DNA repair. By displaying different mechanisms of action, both nanoMOFs and incorporated Gem-MP contribute to improve radiation efficacy. The radiation enhancement factor of Gem-MP loaded nanoMOFs reaches 1.8, one of the highest values ever reported. These results pave the way toward the design of engineered nanoparticles in which each component plays a role in cancer treatment by radiotherapy.
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Usami, N., Usami N, Hirayama, R., Hirayama R, Kobayashi, K., Kobayashi K, Furusawa, Y., Furusawa Y, Le Sech, C., & Le Sech C. (2020). Combination of agents modifying effects in hadrontherapy: modelization of the role of HO degrees free radicals..
Résumé: Purpose: A study is presented of the irradiation of cancerous cervical cell line HeLa loaded with a platinum salt, betamethasone and deoxyglucose. The presence of the platinum increases the free-radical concentration and augments the cell death rate, whereas betamethasone or deoxyglucose induces radiosensitization by the alteration of metabolic pathways. Two by two combinations of these chemicals are made to investigate the possible benefit when two radiosensitizers are present. A model is proposed to understand the results of the presence of two modifying agents on the dose effects.Materials and methods: The cells were incubated for 6 h in the presence of the following molecules: dichloro terpyridine platinum, concentration C = 350 muM, betamethasone and deoxyglucose with concentrations of C = 0.2 muM and C = 6 mM, respectively. The cells were subsequently irradiated by carbon C(6+) ion 290 MeV/amu up to a dose of 2.5 Gy, under atmospheric conditions.Results: The presence of the platinum salt or bethamethasone augments the cell death rate. The combination of betamethasone with the platinum salt also increases the cell death rate, but less than for the platinum salt alone. The explanation is that any radiosensitizer also behaves as a scavenger of free radicals. This dual behavior should be considered in any optimization of the design of radiosensitizers when different ionizing particles are used.
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2018 |
Kuncic, Z., & Lacombe, S. (2018). Nanoparticle radio-enhancement: principles, progress and application to cancer treatment. Physics In Medicine And Biology, 63(2).
Résumé: Enhancement of radiation effects by high-atomic number nanoparticles (NPs) has been increasingly studied for its potential to improve radiotherapeutic efficacy. The underlying principle of NP radio-enhancement is the potential to release copious electrons into a nanoscale volume, thereby amplifying radiation-induced biological damage. While the vast majority of studies to date have focused on gold nanoparticles with photon radiation, an increasing number of experimental, theoretical and simulation studies have explored opportunities offered by other NPs (e.g. gadolinium, platinum, iron oxide, hafnium) and other therapeutic radiation sources such as ion beams. It is thus of interest to the research community to consolidate findings from the different studies and summarise progress to date, as well as to identify strategies that offer promising opportunities for clinical translation. This is the purpose of this Topical Review.
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2017 |
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Falk, M., Stefancikova, L., Lacombe, S., Salado, D., Porcel, E., Pagacova, E., Tillement, O., Lux, F., Depes, D., Falkova, I., Bacikova, A., & Kozubek, S. (2017). Radiosensitization of resistant (Head and Neck) tumor cells by metal nanoparticles. In Febs Journal (Vol. 284, p. 255).
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Lacombe, S., Porcel, E., & Scifoni, E. (2017). Particle therapy and nanomedicine: state of art and research perspectives. Cancer nanotechnology, 8(1), 9.
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2016 |
Izumi, Y., Fujii, K., Wien, F., Houee-Levin, C., Lacombe, S., Salado-Leza, D., Porcel, E., Masoud, R., Yamamoto, S., Refregiers, M., du Penhoat, M. A. H., & Yokoya, A. (2016). Structure Change from beta-Strand and Turn to alpha-Helix in Histone H2A-H2B Induced by DNA Damage Response. Biophysical Journal, 111(1), 69–78.
Résumé: Using synchrotron radiation-based circular dichroism spectroscopy, we found that the DNA damage response induces an increase of alpha-helix structure and a decrease of beta-strand and turn structures in histone H2A-H2B extracted from x-irradiated human HeLa cells. The structural alterations correspond to the assumption that an average of eight amino acid residues form new alpha-helix structures at 310 K. We propose the structural transition from beta-strand and turn structures to an a-helix structure in H2A-H2B as a novel, to our knowledge, process involved in the DNA damage response.
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Schlatholter, T., Eustache, P., Porcel, E., Salado, D., Stefancikova, L., Tillement, O., Lux, F., Mowat, P., Biegun, A. K., van Goethem, M. J., Remita, H., & Lacombe, S. (2016). Improving proton therapy by metal-containing nanoparticles: nanoscale insights. International Journal Of Nanomedicine, 11, 1549–1556.
Résumé: The use of nanoparticles to enhance the effect of radiation-based cancer treatments is a growing field of study and recently, even nanoparticle-induced improvement of proton therapy performance has been investigated. Aiming at a clinical implementation of this approach, it is essential to characterize the mechanisms underlying the synergistic effects of nanoparticles combined with proton irradiation. In this study, we investigated the effect of platinum- and gadolinium-based nanoparticles on the nanoscale damage induced by a proton beam of therapeutically relevant energy (150 MeV) using plasmid DNA molecular probe. Two conditions of irradiation (0.44 and 3.6 keV/mu m) were considered to mimic the beam properties at the entrance and at the end of the proton track. We demonstrate that the two metal-containing nanoparticles amplify, in particular, the induction of nanosize damages (>2 nm) which are most lethal for cells. More importantly, this effect is even more pronounced at the end of the proton track. This work gives a new insight into the underlying mechanisms on the nanoscale and indicates that the addition of metal-based nanoparticles is a promising strategy not only to increase the cell killing action of fast protons, but also to improve tumor targeting.
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Stefancikova, L., Lacombe, S., Salado, D., Porcel, E., Pagacova, E., Tillement, O., Lux, F., Depes, D., Kozubek, S., & Falk, M. (2016). Effect of gadolinium-based nanoparticles on nuclear DNA damage and repair in glioblastoma tumor cells. Journal Of Nanobiotechnology, 14.
Résumé: Background: Tumor targeting of radiotherapy represents a great challenge. The addition of multimodal nanoparticles, such as 3 nm gadolinium-based nanoparticles (GdBNs), has been proposed as a promising strategy to amplify the effects of radiation in tumors and improve diagnostics using the same agents. This singular property named theranostic is a unique advantage of GdBNs. It has been established that the amplification of radiation effects by GdBNs appears due to fast electronic processes. However, the influence of these nanoparticles on cells is not yet understood. In particular, it remains dubious how nanoparticles activated by ionizing radiation interact with cells and their constituents. A crucial question remains open of whether damage to the nucleus is necessary for the radiosensitization exerted by GdBNs (and other nanoparticles). Methods: We studied the effect of GdBNs on the induction and repair of DNA double-strand breaks (DSBs) in the nuclear DNA of U87 tumor cells irradiated with.-rays. For this purpose, we used currently the most sensitive method of DSBs detection based on high-resolution confocal fluorescence microscopy coupled with immunodetection of two independent DSBs markers. Results: We show that, in the conditions where GdBNs amplify radiation effects, they remain localized in the cytoplasm, i.e. do not penetrate into the nucleus. In addition, the presence of GdBNs in the cytoplasm neither increases induction of DSBs by.-rays in the nuclear DNA nor affects their consequent repair. Conclusions: Our results suggest that the radiosensitization mediated by GdBNs is a cytoplasmic event that is independent of the nuclear DNA breakage, a phenomenon commonly accepted as the explanation of biological radiation effects. Considering our earlier recognized colocalization of GdBNs with the lysosomes and endosomes, we revolutionary hypothesize here about these organelles as potential targets for (some) nanoparticles. If confirmed, this finding of cytoplasmically determined radiosensitization opens new perspectives of using nano-radioenhancers to improve radiotherapy without escalating the risk of pathologies related to genetic damage.
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2014 |
Porcel, E., Tillement, O., Lux, F., Mowat, P., Usami, N., Kobayashi, K., Furusawa, Y., Le Sech, C., Li, S., & Lacombe, S. (2014). Gadolinium-based nanoparticles to improve the hadrontherapy performances. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, 10(8), 1601–1608.
Résumé: Nanomedicine is proposed as a novel strategy to improve the performance of radiotherapy. High-Z nanoparticles are known to enhance the effects of ionizing radiation. Recently, multimodal nanoparticles such as gadolinium-based nanoagents were proposed to amplify the effects of x-rays and g-rays and to improve MRI diagnosis. For tumors sited in sensitive tissues, childhood cases and radioresistant cancers, hadrontherapy is considered superior to x-rays and g-rays. Hadrontherapy, based on fast ion radiation, has the advantage of avoiding damage to the tissues behind the tumor; however, the damage caused in front of the tumor is its major limitation. Here, we demonstrate that multimodal gadolinium-based nanoparticles amplify cell death with fast ions used as radiation. Molecular scale experiments give insights into the mechanisms underlying the amplification of radiation effects. This proof-of-concept opens up novel perspectives for multimodal nanomedicine in hadrontherapy, ultimately reducing negative radiation effects in healthy tissues in front of the tumor. From the Clinical Editor: Gadolinium-chelating polysiloxane nanoparticles were previously reported to amplify the anti-tumor effects of x-rays and g-rays and to serve as MRI contrast agents. Fast ion radiation-based hadrontherapy avoids damage to the tissues behind the tumor, with a major limitation of tissue damage in front of the tumor. This study demonstrates a potential role for the above nanoagents in optimizing hadrontherapy with preventive effects in healthy tissue and amplified cell death in the tumor. (C) 2014 Elsevier Inc. All rights reserved.
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Sancey, L., Lux, F., Kotb, S., Roux, S., Dufort, S., Bianchi, A., Cremillieux, Y., Fries, P., Coll, J. - L., Rodriguez-Lafrasse, C., Janier, M., Dutreix, M., Barberi-Heyob, M., Boschetti, F., Denat, F., Louis, C., Porcel, E., Lacombe, S., Le Duc, G., Deutsch, E., Perfettini, J. - L., Detappe, A., Verry, C., Berbeco, R., Butterworth, K. T., McMahon, S. J., Prise, K. M., Perriat, P., & Tillement, O. (2014). The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy. The British journal of radiology, 87(1041).
Résumé: A new efficient type of gadolinium-based theranostic agent (AGuIX) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed.
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Štefančíková L., P. E., Eustache P., Li S., Salado D., Marco S., Guerquin-Kern J.L., Réfrégiers M., Tillement O., Lux F., and Lacombe S. (2014). Cell localisation of gadolinium-based nanoparticles and related radiosensitising efficacy in glioblastoma cells. Cancer Nanotechnology. Cancer Nanotechnology, 5(1), 6.
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2012 |
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Le Sech, C., Kobayashi, K., Usami, N., Furusawa, Y., Porcel, E., & Lacombe, S. (2012). Comment on “Enhanced relative biological effectiveness of proton radiotherapy in tumor cells with internalized gold nanoparticles” [Appl. Phys. Lett. 98, 193702 (2011)]. APPLIED PHYSICS LETTERS, 100(2), 026101.
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Le Sech, C., Kobayashi, K., Usami, N., Furusawa, Y., Porcel, E., & Lacombe, S. (2012). Comment on 'Therapeutic application of metallic nanoparticles combined with particle-induced x-ray emission effect'. Nanotechnology, 23(7), 078002–078001; author reply 078002.
Résumé: A recent paper (Kim et al 2010 Nanotechnology 21 425102) presented results on the combination of irradiation by atomic ions of cells loaded by particles made of heavy atoms. They propose that the projectile induced x-rays emission (PIXE) mechanism has an important contribution to the enhancement of the cell death rate. Experiments made in our group to study the effects of such a combination have shown that the Auger effect induced in the high-Z atoms and the following induction of surrounding water radiolysis has an important contribution to the enhancement of the cell death rate. In the light of our studies we propose an alternative interpretation of the results presented in the paper by Kim et al.
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Porcel, E., Li, S., Usami, N., Remita, H., Furusawa, Y., Kobayashi, K., Le Sech, C., & Lacombe, S. (2012). Nano-Sensitization under gamma rays and fast ion radiation. In 1ST NANO-IBCT CONFERENCE 2011 – RADIATION DAMAGE OF BIOMOLECULAR SYSTEMS: NANOSCALE INSIGHTS INTO ION BEAM CANCER THERAPY (Vol. 373).
Résumé: The use of heavy compounds to enhance radiation induced damage is a promising approach to improve the therapeutic index of radiotherapy. In order to quantify and control the effects of these radiosensitizers, it is of fundamental interest to describe the elementary processes which take place at the molecular level. Using DNA as a probe, we present a comparison of the damage induced in the presence of platinum compounds exposed to different types of ionizing radiation. We present the results obtained with gamma rays (Linear Energy Transfer (LET) = 0.2 keV.mu m(-1)), fast helium ions He2+ (LET = 2.3 keV.mu m(-1)) and fast carbon ions C6+ (LET = 13 keV.mu m(-1) and LET=110 keV.mu m(-1)). The efficiency of two different sensitizers was measured: platinum based molecules (the chloroterpyridine platinum – PtTC) and platinum nanoparticles (PtNP). These experiments show that the two sensitizers are efficiently amplifying molecular damage under photon or ion irradiation. Experiments with a radical scavenger confirmed that these damages are mediated by free radicals for more than 90%. More interestingly, the induction of complex damage, the most lethal for the cells, is amplified by a factor of 1.5 on average if platinum (PtTC and PtNP) is present. As already known, the induction of complex damages increases also with the radiation LET. So, finally, the most significant enhancement of complex damage is observed when ion radiation is combined with platinum induced sensitization.
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Sarsa, A., & Le Sech, C. (2012). Quantum confinement study of the H-2(+) ion with the Monte Carlo approach. Respective role of electron and nuclei confinement. JOURNAL OF PHYSICS B-ATOMIC MOLECULAR AND OPTICAL PHYSICS, 45(20), 205101.
Résumé: A simple approximate trial wavefunction is used to study, within a variational approach and beyond the Born-Oppenheimer approximation, the molecular ion H-2(+) confined by impenetrable spherical surfaces. This wavefunction describes explicitly the motion of the nuclei and the electron of this three-body system in its lowest rovibrational state. Two cut-off functions are introduced to fulfil the Dirichlet boundary conditions, respectively, for the electron and the nuclei. The results show an increase of the energy of the ion when both the confinement radius r(ce) of the electron and R-cN of the nuclei become smaller. The electron constraint is found to be much more efficient to increase the energy than the nuclei confinement. This study shows that a metastable bound state of the ion, above the energy corresponding to the dissociation limit, can be obtained when the electron constraint is present. Expectation values of the internuclear and electron-to-origin distances are also calculated and show a rapid decrease when the confinement is stronger. Finally, the quantum pressure versus the confinement radius is also estimated. A rapid rise of the pressure value when r(ce) is less than 3 au is observed.
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2011 |
Constans, J. M., Collet, S., Guillamo, J. S., Hossu, G., Lacombe, S., Gauduel, Y. A., Levin, C. H., Dou, W., Ruan, S., Barre, L., Rioult, F., Derlon, J. M., Lechapt-Zalcman, E., Valable, S., Chapon, F., Courtheoux, P., Fong, V., & Kauffmann, F. (2011). Effects of reactive oxygen species on metabolism monitored by longitudinal H-1 single voxel MRS follow-up in patients with mitochondrial disease or cerebral tumors. In COST CHEMISTRY CM0603-MELUSYN JOINT MEETING: DAMAGES INDUCED IN BIOMOLECULES BY LOW AND HIGH ENERGY RADIATIONS (Vol. 261).
Résumé: Free radicals, or Reactive Oxygen Species (ROS), have an effect on energy and glycolytic metabolism, mitochondrial function, lipid metabolism, necrosis and apoptosis, cell proliferation, and infiltration. These changes could be monitored longitudinally (every 4 months over 6 years) in humans with glial brain tumors (low and high grade) after therapy, using conventional magnetic resonance imaging (MRI) and spectroscopy (MRS) and MR perfusion. Some examples of early clinical data from longitudinal follow-up monitoring in humans of energy and glycolytic metabolism, lipid metabolism, necrosis, proliferation, and infiltration measured by conventional MRI, MRS and perfusion, and positron emission tomography (PET) are shown in glial brain tumors after therapy. Despite the difficulty, the variability and unknown factors, these repeated measurements give us a better insight into the nature of the different processes, tumor progression and therapeutic response.
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Parent, P., Laffon, C., Bournel, F., Lasne, J., & Lacombe, S. (2011). NEXAFS: a unique tool to follow the photochemistry of small organic molecules in condensed water. In COST CHEMISTRY CM0603-MELUSYN JOINT MEETING: DAMAGES INDUCED IN BIOMOLECULES BY LOW AND HIGH ENERGY RADIATIONS (Vol. 261).
Résumé: Soft X ray induced chemistry of simple organic molecules as carbon monoxide (CO), methanol (CH(3)OH) and glycine (NH(3)CH(2)COOH) in water and nitric acid hydrate has been investigated with NEXAFS spectroscopy. In the pure species, extremely high survival rates are observed, a consequence of the back reactions allowed in the condensed phase. When mixed with water, the survival rates are considerably reduced by reaction with the hydroxyl radical (OH). The formation of CO(2) is also enhanced at the expense of CO, the main byproduct in the photolysis of the pure species. Finally, it is shown that water plays no role in the destruction of the amino acid.
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Porcel, E., Kobayashi, K., Usami, N., Remita, H., Le Sech, C., & Lacombe, S. (2011). Photosensitization of plasmid-DNA loaded with platinum nano-particles and irradiated by low energy X-rays. In COST CHEMISTRY CM0603-MELUSYN JOINT MEETING: DAMAGES INDUCED IN BIOMOLECULES BY LOW AND HIGH ENERGY RADIATIONS (Vol. 261).
Résumé: Damage in DNA plasmids (pBR322) loaded with platinum nanoparticles (NP-Pt) DNA-NP and irradiated with monochromatic X-rays tuned to the resonant photoabsorption energy of the L(III) and M(III) electronic inner-shell of platinum – respectively 11556 eV and 2649 eV – and off-resonant X-rays – 11536 eV and 2639 eV- is investigated. In all the experiments, an enhancement of the single and double strand break – SSB and DSB – yields is observed when NP-Pt are present. Amplification effects are almost similar for the irradiations performed at on and off the L or M shell resonance suggesting that a non resonant mechanism is responsible for the major part of the DNA breaks enhancement. The amount of DNA breaks measured in the present work is compared to the results in similar experiments made with complexes of plasmid-DNA containing platinum molecule : chloroterpyridine platinum (PtTC). The average number of PtTC molecules in the solution is the same as in the experiments made with NP-Pt in order to study a possible difference in the radiosensitization efficiency when the high-Z atoms are clustered (NP-Pt) or dispersed in the system (PtTC). A mechanism is suggested involving photoelectrons which can efficiently ionize the platinum atoms. These results are consistent with those observed when DNA-NP complexes are irradiated by fast atomic ions. These findings suggest that any nanoparticle made of high-Z atoms might behaves as radiation enhancer whatever the ionizing radiation is electromagnetic or charged particle source.
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Ros, D., Cassou, K., Cros, B., Daboussi, S., Demailly, J., Guilbaud, A., Kazamias, S., Lagron, J. - C., Maynard, G., Neveu, O., Pittman, M., Zielbauer, B., Zimmer, D., Kuhl, T., Lacombe, S., Porcel, E., du Penhoat, M. - A., Zeitoun, P., & Mourou, G. (2011). LASERIX: An open facility for developments of EUV and soft X-ray lasers and applications-Developments of XUV sources using high power laser facilities: ILE, ELI. NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT, 653(1), 76–79.
Résumé: LASERIX is a high-power laser facility leading to High-repetition-rate XUV laser pumped by Titanium:Sapphire laser. The aim of this laser facility is to offer Soft XRLs in the 30-7 nm range and auxiliary IR beam, which could also be used to produce synchronized XUV sources. In this contribution, the main results concerning both the development of XUV sources and their use for applications (irradiation of DNA samples) are presented, as well the present status and some perspectives for LASERIX. (C) 2011 Elsevier B.V. All rights reserved.
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Sarsa, A., & Le Sech, C. (2011). Variational Monte Carlo Method with Dirichlet Boundary Conditions: Application to the Study of Confined Systems by Impenetrable Surfaces with Different Symmetries. JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 7(9), 2786–2794.
Résumé: Variational Monte Carlo method is a powerful tool to determine approximate wave functions of atoms, molecules, and solids up to relatively large systems. In the present work, we extend the variational Monte Carlo approach to study confined systems. Important properties of the atoms, such as the spatial distribution of the electronic charge, the energy levels, or the filling of electronic shells, are modified under confinement. An expression of the energy very similar to the estimator used for free systems is derived. This opens the possibility to study confined systems with little changes in the solution of the corresponding free systems. This is illustrated by the study of helium atom in its ground state (1)S and the first (3)S excited state confined by spherical, cylindrical, and plane impenetrable surfaces. The average interelectronic distances are also calculated. They decrease in general when the confinement is stronger; however, it is seen that they present a minimum for excited states under confinement by open surfaces (cylindrical, planes) around the radii values corresponding to ionization. The ground (2)S and the first (2)P and (2)D excited states of the lithium atom are calculated under spherical constraints for different confinement radii. A crossing between the (2)S and (2)P states is observed around r(c) = 3 atomic units, illustrating the modification of the atomic energy level under confinement. Finally the carbon atom is studied in the spherical symmetry by using both variational and diffusion Monte Carlo methods. It is shown that the hybridized state sp(3) becomes lower in energy than the ground state (3)P due to a modification and a mixing of the atomic orbitals s, p under strong confinement. This result suggests a model, at least of pedagogical interest, to interpret the basic properties of carbon atom in chemistry.
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2010 |
Kobayashi, K., Usami, N., Porcel, E., Lacombe, S., & Le Sech, C. (2010). Enhancement of radiation effect by heavy elements. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 704(1-3), 123–131.
Résumé: The enhancement of radiobiological effects by heavy elements is reviewed. As an underlying mechanism, Auger effects have been stressed which can be induced via inner-shell photoabsorption or via excitation and/or ionization by secondary electrons. Latter channel of Auger induction expands the applicability of Auger enhancing phenomena to electron and hadron therapy. After discussion on the required characteristics for radiosensitizers, possibility of nanoparticles of Au or Pt is mentioned since they could be synthesized or modified as ideal radiosensitizers. (C) 2010 Elsevier B.V. All rights reserved.
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Lacombe, S., Sabatier, L., Wien, F., & Gauduel, Y. A. (2010). Spatio-temporal radiation biology: new insights and biomedical perspectives. CELL DEATH & DISEASE, 1.
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Laffon, C., Lasne, J., Bournel, F., Schulte, K., Lacombe, S., & Parent, P. (2010). Photochemistry of carbon monoxide and methanol in water and nitric acid hydrate ices: A NEXAFS study. PHYSICAL CHEMISTRY CHEMICAL PHYSICS, 12(36), 10865–10870.
Résumé: Soft X-ray induced chemistry of H(2)O, CO and CH(3)OH and the effects of the water and nitric acid hydrate (HNO(3)center dot 1.65H(2)O) matrix on the photochemistry of CO and CH(3)OH have been investigated using NEXAFS spectroscopy. For pure H(2)O, CO and CH(3)OH ices, we show that the destruction rates are strongly limited by back reactions, leading to strikingly high survival rates of these molecules upon the harsh irradiation conditions to which they are submitted. We also evidence the interplay between the photochemical reactions of CO and CH(3)OH and those of the matrix. The OH and O radicals released by the photolysis of H(2)O and HNO(3) react with the CO and CH(3)OH and their fragments, considerably reducing the survival rates compared to pure CO and pure CH(3)OH ices, especially in presence of nitric acid, and dramatically enhancing the formation of CO(2) at the expense of CO. Because NEXAFS spectroscopy allows identifying which reactions are important among those possible, it emerges a simple picture of the photochemical routes of CO and CH(3)OH in the H(2)O and HNO(3)/H(2)O environments.
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Porcel, E., Liehn, S., Remita, H., Usami, N., Kobayashi, K., Furusawa, Y., Le Sech, C., & Lacombe, S. (2010). Platinum nanoparticles: a promising material for future cancer therapy? Nanotechnology, 21(8), 85103.
Résumé: Recently, the use of gold nanoparticles as potential tumor selective radiosensitizers has been proposed as a breakthrough in radiotherapy. Experiments in living cells and in vivo have demonstrated the efficiency of the metal nanoparticles when combined with low energy x-ray radiations (below conventional 1 MeV Linac radiation). Further studies on DNA have been performed in order to better understand the fundamental processes of sensitization and to further improve the method. In this work, we propose a new strategy based on the combination of platinum nanoparticles with irradiation by fast ions effectively used in hadron therapy. It is observed in particular that nanoparticles enhance strongly lethal damage in DNA, with an efficiency factor close to 2 for double strand breaks. In order to disentangle the effect of the nano-design architecture, a comparison with the effects of dispersed metal atoms at the same concentration has been performed. It is thus shown that the sensitization in nanoparticles is enhanced due to auto-amplified electronic cascades inside the nanoparticles, which reinforces the energy deposition in the close vicinity of the metal. Finally, the combination of fast ion radiation (hadron therapy) with platinum nanoparticles should strongly improve cancer therapy protocols.
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Usami, N., Kobayashi, K., Hirayama, R., Furusawa, Y., Porcel, E., Lacombe, S., & Le Sech, C. (2010). Comparison of DNA Breaks at Entrance Channel and Bragg Peak Induced by Fast C6+ Ions-Influence of the Addition of Platinum Atoms on DNA. JOURNAL OF RADIATION RESEARCH, 51(1), 21–26.
Résumé: When energetic carbon ion beam (GeV range) goes through the matter, inelastic processes such as electronic ionization, molecular and nuclear fragmentation occur. For carbontherapy (hadrontherapy) purpose, it is of interest to compare the number of DNA breaks -single SSB or double DSB- for a given dose at the entrance channel and at the Bragg peak to look for a possible differential effect in the number of DNA breaks induced at these two locations. Samples of free plasmids DNA and complexes of plasmids DNA added with molecules containing platinum have been placed at different locations of an experimental setup simulating penetration depths of the ion beam in water and irradiated by carbon ions 290 MeV/amu. The DNA breaks have been quantified by subsequent electrophoresis on agarose gels. To disentangle the respective role of the direct and indirect effect, a free radical scavenger of hydroxyl radicals HO degrees -dimethyl sulfoxide DMSO- has been added in some of the experiments. In the range of Linear Energy Transfert -LET 13 – 110 keV/mu m-, the number of the DSB was found to be constant versus the LET for a given dose. Contrary, the number of the SSB decreases at the Bragg peak compared to the entrance channel. In the presence of platinum, the number of single and double breaks was considerably enhanced, and follows a similar behaviour than in the free-DNA experiments. Quantitative results on DNA damages do not show significant enhancement due to the nuclear or to the molecular fragmentation in the present experiments.
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2009 |
Lacombe, S., & Le Sech, C. (2009). Advances in radiation biology: Radiosensitization in DNA and living cells. SURFACE SCIENCE, 603(10-12), 1953–1960.
Résumé: One fundamental goal of radiation biology is the evolution of concepts and methods for the elaboration of new approaches and protocols for the treatment of cancers. In this context, the use of fast ions as ionizing particles offers the advantage of optimizing cell killing inside the tumor whilst preserving the surrounding healthy tissues. One extremely promising strategy investigated recently is the addition of radiosensitizers in the targeted tissue. The optimization of radiotherapy with fast ions implies a multidisciplinary approach to ionizing radiation effects on complex living systems, ranging from studies on single molecules to investigations of entire organisms. In this article we review recent studies on ion induced damages in simple and complex biological systems, from DNA to living cells. The specific aspect of radiosensitization induced by metallic atoms is described. As a fundamental result, the addition of sensitizing compounds with ion irradiation may improve therapeutic index in cancer therapy. In conclusion, new perspectives are proposed based on the experience and contribution of different communities including Surface Sciences, to improve the development of radiation biology. (C) 2009 Elsevier B.V. All rights reserved.
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Parent, P., Bournel, F., Lasne, J., Lacombe, S., Strazzulla, G., Gardonio, S., Lizzit, S., Kappler, J. - P., Joly, L., Laffon, C., & Carniato, S. (2009). The irradiation of ammonia ice studied by near edge x-ray absorption spectroscopy. JOURNAL OF CHEMICAL PHYSICS, 131(15), 154308.
Résumé: A vapor-deposited NH(3) ice film irradiated at 20 K with 150 eV photons has been studied with near-edge x-ray absorption fine structure (NEXAFS) spectroscopy at the nitrogen K-edge. Irradiation leads to the formation of high amounts (12%) of molecular nitrogen N(2), whose concentration as a function of the absorbed energy has been quantified to 0.13 molecule/eV. The stability of N(2) in solid NH(3) has been also studied, showing that N(2) continuously desorbs between 20 and 95 K from the irradiated ammonia ice film. Weak concentrations (<1%) of other photoproducts are also detected. Our NEXAFS simulations show that these features own to NH(2), N(2)H(2), and N(3)(-).
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Ros, D., Kazamias, S., Guilbaud, O., Habib, J., Zielbauer, B., Pittman, M., Jamelot, G., Klisnick, A., Lagron, J. - C., Joyeux, D., de Rossi, S., Delmotte, F., Lacombe, S., Porcel, E., Lesech, C., Penhoat, A. M., & Touati, A. (2009). Recent Advances on LASERIX Facility: Development of XUV Sources System and Applications. Perspectives from 2008 to 2010. In X-RAY LASERS 2008 (Vol. 130, pp. 13–22).
Résumé: LASERIX is a high-power laser facility leading to High-repetition-rate XUV laser pumped by Titanium:Sapphire laser. The aim of this laser facility is to offer Soft XRLs in the 30-7 nm range and auxiliary IR beam that could also be used to produce synchronized XUV sources. This experimental configuration highly enhances the scientific opportunities of the facility, giving thus the opportunity to realize both X-ray laser experiments and more generally pump/probe experiments, mixing IR and XUV sources. In this contribution, the main results concerning both the development of XUV sources (in the seeded or ASE mode) and their use for applications (irradiation of DNA samples) are presented.
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Zielbauer, B., Habib, J., Kazamias, S., Guilbaud, O., Pittman, M., Ros, D., du Penhoat, M. - A. H., Touati, A., Le Sech, C., Porcel, E., & Lacombe, S. (2009). Strand Breaks in DNA Samples Induced with LASERIX. In X-RAY LASERS 2008 (Vol. 130, pp. 409–415).
Résumé: Samples of plasmid DNA were irradiated with pulsed 18.9 nm radiation originating from a Mo X-ray laser pumped in GRIP configuration at the LASERIX facility [1]. Surface doses of up to 500 kGray were delivered with a repetition rate of 10 Hz and average pulse energy of 200 nJ. The occurrence of single and double strand breaks not present in controls having undergone the same treatment except for the XRL irradiation can be seen as a clear effect of the XRL irradiation. This confirms the role of direct effects in DNA damages as previously seen with low energy ions [2, 3] and electrons.
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2008 |
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Guilbaud, O., Ros, D., Kazamias, S., Zielbauer, B., Habib, J., Pittman, M., Cassou, K., Ple, F., Farinet, M., Klisnick, A., de Dortan, F., Lacombe, S., Porcel, E., Le Sech, C., du Penhoat, M. - A., Touati, A., Marsi, M., Fajardo, M., Zeitoun, P., & Joyeux, D. (2008). LASERIX: first record from the plant. In UVX 2008: 9E COLLOQUE SUR LES SOURCES COHERENTES ET INCOHERENTES UV (pp. 57–63).
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