Alexander P Klapproth1,2, Jan Schuemann3,4, Stefan Stangl1, Tianwu Xie5,6, Wei Bo Li2, Gabriele Multhoff1. 1. Center for Translational Cancer Research Technische Universität München (TranslaTUM), Klinikum rechts der Isar, München, Germany. 2. Institute of Radiation Medicine, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany. 3. Physics Division, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, United States of America. 4. Harvard Medical School, Boston, MA 02115, United States of America. 5. Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, Geneva, Switzerland. 6. Institute of Radiation Medicine, Fudan University, Shanghai, China.
Abstract
Background: Gold nanoparticles (AuNPs) are considered as promising agents to increase the radiosensitivity of tumor cells. However, the biological mechanisms of radiation enhancement effects of AuNPs are still not well understood. We present a multi-scale Monte Carlo simulation framework within TOPAS-nBio to investigate the increase of DNA damage due to the presence of AuNPs in mouse tumor models. Methods: A tumor was placed inside a voxel mouse model and irradiated with either 100 kVp or 200 kVp x-ray beams. Phase spaces were employed to transfer particles from the macroscopic (voxel) scale to the microscopic scale, which consists of a cell geometry including a detailed mouse DNA model. Radiosensitizing effects were calculated in the presence and absence of hybrid nanoparticles with a Fe2O3 core surrounded by a gold layer (AuFeNPs). To simulate DNA damage even for very small energy tracks, Geant4-DNA physics and chemistry models were used on microscopic scale. Results: An AuFeNP induced enhancement of both dose and DNA strand breaks has been established for different scenarios. Produced chemical radicals including hydroxyl molecules, which were assumed to be responsible for DNA damage through chemical reactions, were found to be significantly increased. We further observed a dependency of the results on the location of the cells within the tumor for 200 kVp x-ray beams. Conclusions: Our multi-scale approach allows to study irradiation induced physical and chemical effects on cells. We showed a potential increase in cell radiosensitization caused by relatively small concentrations of AuFeNPs. Our new methodology allows the individual adjustment of parameters in each simulation step and therefore can be used for other studies investigating the radiosensitizing effects of AuFeNPs or AuNPs in living cells.
Background: Gold nanoparticles (AuNPs) are considered as promising agents to increase the radiosensitivity of tumor cells. However, the biological mechanisms of radiation enhancement effects of AuNPs are still not well understood. We present a multi-scale Monte Carlo simulation framework within TOPAS-nBio to investigate the increase of DNA damage due to the presence of AuNPs in mouse tumor models. Methods: A tumor was placed inside a voxel mouse model and irradiated with either 100 kVp or 200 kVp x-ray beams. Phase spaces were employed to transfer particles from the macroscopic (voxel) scale to the microscopic scale, which consists of a cell geometry including a detailed mouse DNA model. Radiosensitizing effects were calculated in the presence and absence of hybrid nanoparticles with a Fe2O3 core surrounded by a gold layer (AuFeNPs). To simulate DNA damage even for very small energy tracks, Geant4-DNA physics and chemistry models were used on microscopic scale. Results: An AuFeNP induced enhancement of both dose and DNA strand breaks has been established for different scenarios. Produced chemical radicals including hydroxyl molecules, which were assumed to be responsible for DNA damage through chemical reactions, were found to be significantly increased. We further observed a dependency of the results on the location of the cells within the tumor for 200 kVp x-ray beams. Conclusions: Our multi-scale approach allows to study irradiation induced physical and chemical effects on cells. We showed a potential increase in cell radiosensitization caused by relatively small concentrations of AuFeNPs. Our new methodology allows the individual adjustment of parameters in each simulation step and therefore can be used for other studies investigating the radiosensitizing effects of AuFeNPs or AuNPs in living cells.
Authors: Wonmo Sung; Sung-Joon Ye; Aimee L McNamara; Stephen J McMahon; James Hainfeld; Jungwook Shin; Henry M Smilowitz; Harald Paganetti; Jan Schuemann Journal: Nanoscale Date: 2017-05-11 Impact factor: 7.790
Authors: Erez Lieberman-Aiden; Nynke L van Berkum; Louise Williams; Maxim Imakaev; Tobias Ragoczy; Agnes Telling; Ido Amit; Bryan R Lajoie; Peter J Sabo; Michael O Dorschner; Richard Sandstrom; Bradley Bernstein; M A Bender; Mark Groudine; Andreas Gnirke; John Stamatoyannopoulos; Leonid A Mirny; Eric S Lander; Job Dekker Journal: Science Date: 2009-10-09 Impact factor: 47.728