TY - JOUR A1 - Hahn, Marc Benjamin T1 - Accessing radiation damage to biomolecules on the nanoscale by particle-scattering simulations N2 - Radiation damage to DNA plays a central role in radiation therapy to cure cancer. The physico-chemical and biological processes involved encompass huge time and spatial scales. To obtain a comprehensive understanding on the nano and the macro scale is a very challenging tasks for experimental techniques alone. Therefore particle-scattering simulations are often applied to complement measurements and aide their interpretation, to help in the planning of experiments, to predict their outcome and to test damage models. In the last years, powerful multipurpose particle-scattering framework based on the Monte-Carlo simulation (MCS) method, such as Geant4 and Geant4-DNA, were extended by user friendly interfaces such as TOPAS and TOPAS-nBio. This shifts their applicability from the realm of dedicated specialists to a broader range of scientists. In the present review we aim to give an overview over MCS based approaches to understand radiation interaction on a broad scale, ranging from cancerous tissue, cells and their organelles including the nucleus, mitochondria and membranes, over radiosensitizer such as metallic nanoparticles, and water with additional radical scavenger, down to isolated biomolecules in the form of DNA, RNA, proteins and DNA-protein complexes. Hereby the degradation of biomolecules by direct damage from inelastic scattering processes during the physical stage, and the indirect damage caused by radicals during the chemical stage as well as some parts of the early biological response is covered. Due to their high abundance the action of hydroxyl radicals (•OH) and secondary low energy electrons (LEE) as well as prehydrated electrons are covered in additional detail. Applications in the prediction of DNA damage, DNA repair processes, cell survival and apoptosis, influence of radiosensitizer on the dose distribution within cells and their organelles, the study of linear energy transfer (LET), the relative biological effectiveness (RBE), ion beam cancer therapy, microbeam radiation therapy (MRT), the FLASH effect, and the radiation induced bystander effect are reviewed. KW - DNA KW - Protein KW - G5P KW - OH KW - Au KW - AuNP KW - Radiation KW - SSB KW - DSB KW - Beta decay KW - Brachytherapy KW - Cancer treatment KW - Clustered nanoparticles KW - DNA damage KW - Dosimetry KW - Energy deposit KW - Geant4 KW - Geant4-DNA KW - Gold Nanoparticles KW - Livermore model KW - Low energy electrons KW - MCS KW - Microdosimetry KW - Monte-Carlo simulation KW - NP KW - OH radical KW - Particle scattering KW - Penelope model KW - Proteins KW - Radiation damage KW - Radiation therapy KW - Radiationtherapy KW - Radioactive decay KW - Radiolysis KW - Radiotherapy KW - Simulation KW - TOPAS KW - TOPAS-nbio KW - Base damage KW - Base loss KW - DNA radiation damage KW - Direct damage KW - Dissociative electron attachment (DEA) KW - Dissociative electron transfer (DET) KW - Double-strand break (DSB) KW - ESCA KW - Hydrated DNA KW - Hydrated electron KW - Hydration shell KW - Hydroxyl radical KW - Indirect damage KW - Ionization KW - Ionisation KW - NAP-XPS KW - Near ambient pressure xray photo electron spectroscopy KW - Net-ionization reaction KW - Prehydrated electron KW - Presolvated electron KW - Quasi-direct damage KW - ROS KW - Radical KW - Reactive oxygen species KW - Single-strand break (SSB) KW - XPS KW - Xray KW - Xray photo electron spectrocopy KW - Cosolute KW - Ectoin KW - Ectoine KW - GVP KW - Gene five protein KW - Hydroxyectoine KW - Ionizing radiation damage KW - OH radical scavenger KW - Monte-Carlo simulations KW - Nanodosimetry KW - Osmolyte KW - Particle scattering simulations KW - Protein unfolding KW - Radical Scavenge KW - Radical scavenger KW - Single-stranded DNA-binding proteins KW - SAXS KW - Bio-SAXS KW - X-ray scattering KW - ssDNA KW - dsDNA KW - FLASH effect KW - Bystander effect KW - Ion beam therapy KW - Bragg peak KW - LET KW - MCNP KW - Photons KW - Electrons KW - Carbon ions KW - MRT KW - RNA KW - RBE KW - base loss KW - abasic side KW - DMSO KW - Cells PY - 2023 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-573240 DO - https://doi.org/10.1088/2399-6528/accb3f SN - 2399-6528 VL - 7 IS - 4 SP - 042001 PB - Institute of Physics (IOP) Publishing CY - London AN - OPUS4-57324 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - Combined cell and nanoparticle models for TOPAS to study radiation dose enhancement by Monte-Carlo based particle scattering Simulations N2 - Dose enhancement by gold nanoparticles (AuNP) increases the biological effectiveness of radiation damage in biomolecules and tissue. To apply them effectively during cancer therapy their influence on the locally delivered dose has to be determined.[1] Hereby, the AuNP locations strongly influence the energy deposit in the nucleus, mitochondria, membrane and the cytosol of the targeted cells. To estimate these effects, particle scattering simulations are applied. In general, different approaches for modeling the AuNP and their distribution within the cell are possible. In this work, two newly developed continuous and discrete-geometric models for simulations of AuNP in cells are presented. [2] These models are applicable to simulations of internal emitters and external radiation sources. Most of the current studies on AuNP focus on external beam therapy. In contrast, we apply the presented models in Monte-Carlo particle scattering simulations to characterize the energy deposit in cell organelles by radioactive 198AuNP. They emit beta and gamma rays and are therefore considered for applications with solid tumors. Differences in local dose enhancement between randomly distributed and nucleus targeted nanoparticles are compared. Hereby nucleus targeted nanoparticels showed a strong local dose enhancement in the radio sensitive nucleus. These results are the foundation for ongoing experimental work which aims to obtain a mechanistic understanding of cell death induced by radioactive 198Au. T2 - #RSCposter 2023 CY - Online meeting DA - 28.02.2023 KW - AuNP KW - Beta decay KW - Brachytherapy KW - Cancer treatment KW - Clustered nanoparticles KW - DNA KW - DNA damage KW - Dosimetry KW - Energy deposit KW - Geant4 KW - Geant4-DNA KW - Gold Nanoparticles KW - LEE KW - Livermore model KW - Low energy electrons KW - MCS KW - Microdosimetry KW - Monte-Carlo simulation KW - NP KW - OH radical KW - Penelope model KW - Radiation damage KW - Radiation therapy KW - Radiationtherapy KW - Radiotherapy KW - Radioactive decay KW - Radiolysis KW - Simulation KW - TOPAS KW - TOPAS-nbio KW - beta particle KW - particle scattering PY - 2023 AN - OPUS4-57060 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - Simulaciónes de Montecarlo II: El scoring en las superficies N2 - En esta presentación desarrollaremos un ejemplo de aplicación para la dispersión de partículas utilizando el método de simulación de Monte- Carlo. Se discutirá el caso de las nanopartículas de oro radiactivo y como obtener informacions sobre diferente tipos de particulas pasando las superfices. T2 - Seminar of the bioanalysis group CY - Universidad Nacional de Colombia, Medellin, Colombia DA - 16.03.2020 KW - Geant4 KW - Geant4-DNA KW - MCS KW - Particle scattering simulation KW - Particle scattering simulations KW - Radioactive decay KW - Radioactive nanoparticle KW - Desintegracion radioactiva KW - Geant4 KW - Monte-Carlo simulations KW - Método de Montecarlo KW - Topas KW - nanoparticula PY - 2020 AN - OPUS4-50564 LA - spa AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - Setup of a Particle Scattering Simulation environment N2 - A step by step introduction to the setup of a particle scattering simulation is given. Followed by an installation session. T2 - Seminar of the bioanalysis group CY - Universidad Nacional de Colombia, Medellin, Columbia DA - 12.02.2020 KW - Geant4 KW - Geant4-DNA KW - MCS KW - Monte-Carlo simulations KW - Particle scattering simulations KW - Scattering KW - Simulations KW - Debian KW - Linux KW - Topas KW - C++ KW - Topas-nbio KW - Git KW - Cmake PY - 2020 AN - OPUS4-50366 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - Ejemplos de simulaciónes de Montecarlo La desintegración radioactiva N2 - A walkthrough how to setup radioactive sources in monte-carlo particle scattering simulations and perform different types of scorings. N2 - En esta presentación desarrollaremos un ejemplo de aplicación para la dispersión de partículas utilizando el método de simulación de Monte- Carlo. Se discutirá el caso de las nanopartículas de oro radiactivo y los diferentes tipos del scoring. T2 - Seminar of the bioanalysis group CY - Universidad Nacional de Colombia, Medellin, Columbia DA - 27.02.2020 KW - MCS KW - Geant4-DNA KW - Geant4 KW - Radioactive nanoparticle KW - Radioactive decay KW - Particle scattering simulations KW - Particle scattering simulation KW - Topas KW - Monte-Carlo simulations KW - Desintegracion radioactiva KW - Método de Montecarlo KW - Geant4 KW - nanoparticula PY - 2020 AN - OPUS4-50472 LA - spa AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - Combined cell and nanoparticle models for TOPAS to study radiation dose enhancement by Monte-Carlo based particle scattering Simulations N2 - Dose enhancement by gold nanoparticles (AuNP) increases the biological effectiveness of radiation damage in biomolecules and tissue. To apply them effectively during cancer therapy their influence on the locally delivered dose has to be determined.[1] Hereby, the AuNP locations strongly influence the energy deposit in the nucleus, mitochondria, membrane and the cytosol of the targeted cells. To estimate these effects, particle scattering simulations are applied. In general, different approaches for modeling the AuNP and their distribution within the cell are possible. In this work, two newly developed continuous and discrete-geometric models for simulations of AuNP in cells are presented. [2] These models are applicable to simulations of internal emitters and external radiation sources. Most of the current studies on AuNP focus on external beam therapy. In contrast, we apply the presented models in Monte-Carlo particle scattering simulations to characterize the energy deposit in cell organelles by radioactive 198AuNP. They emit beta and gamma rays and are therefore considered for applications with solid tumors. Differences in local dose enhancement between randomly distributed and nucleus targeted nanoparticles are compared. Hereby nucleus targeted nanoparticels showed a strong local dose enhancement in the radio sensitive nucleus. These results are the foundation for ongoing experimental work which aims to obtain a mechanistic understanding of cell death induced by radioactive 198Au. T2 - NALS 2022 CY - Santander, Spain DA - 27.04.2022 KW - AuNP KW - Beta decay KW - beta particle KW - Brachytherapy KW - Cancer treatment KW - Clustered nanoparticles KW - DNA KW - DNA damage KW - Dosimetry KW - Energy deposit KW - Geant4 KW - Geant4-DNA KW - Gold Nanoparticles KW - LEE KW - Livermore model KW - Low energy electrons KW - MCS KW - Microdosimetry KW - Monte-Carlo simulation KW - NP KW - OH radical KW - particle scattering KW - Penelope model KW - Radiation damage KW - Radiation therapy KW - Radiationtherapy KW - Radioactive decay KW - Radiolysis KW - Simulation KW - TOPAS KW - TOPAS-nbio PY - 2022 AN - OPUS4-54775 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - BP150: Combined cell and nanoparticle models for TOPAS to study radiation dose enhancement by Monte-Carlo based particle scattering Simulations N2 - Dose enhancement by gold nanoparticles (AuNP) increases the biological effectiveness of radiation damage in biomolecules and tissue. To apply them effectively during cancer therapy their influence on the locally delivered dose has to be determined. Hereby, the AuNP locations strongly influence the energy deposit in the nucleus, mitochondria, membrane and the cytosol of the targeted cells. In this work, two newly developed continuous and discrete-geometric models for simulations of AuNP in cells are presented. We apply the presented models in Monte-Carlo particle scattering simulations to characterize the energy deposit in cell organelles by radioactive 198AuNP. They emit beta and gamma rays and are therefore considered for applications with solid tumors. Differences in local dose enhancement between randomly distributed and nucleus targeted nanoparticles are compared. Hereby nucleus targeted nanoparticels showed a strong local dose enhancement in the radio sensitive nucleus. T2 - DPG Frühjahrstagung CY - Dresden, Germany DA - 26.03.2023 KW - AuNP KW - Beta decay KW - Brachytherapy KW - Cancer treatment KW - Clustered nanoparticles KW - DNA KW - DNA damage KW - Dosimetry KW - Energy deposit KW - Geant4 KW - Geant4-DNA KW - Gold Nanoparticles KW - LEE KW - Livermore model KW - Low energy electrons KW - MCS KW - Microdosimetry KW - Monte-Carlo simulation KW - NP KW - OH radical KW - Penelope model KW - Radiation damage KW - Radiation therapy KW - Radiationtherapy KW - Radioactive decay KW - Radiolysis KW - Radiotherapy KW - Simulation KW - TOPAS KW - TOPAS-nbio KW - Beta particle KW - Particle scattering KW - Protein KW - Proteins PY - 2023 AN - OPUS4-57253 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Zutta Villate, J. M. A1 - Viviana Rojas, J. A1 - Hahn, Marc Benjamin A1 - Anselmo Puerta, J. T1 - Synthesis of 198Au nanoparticles sub 10 nm due optimization on local dose by Monte Carlo simulations for cancer treatment N2 - To enhance the biological effects of radiation damage in cancerous cells, we present an alternative approach to the use of gold nanoparticles (AuNP), focusing on the synthesis and characterization of highly monodisperse, spherical radioactive gold nanoparticles 198AuNP. The size of the AuNP size was optimized with the help of Geant4/TOPAS particle scattering simulations, and energy deposition per nm3 per decay for varying radii (2–10 nm) was evaluated. This work is the foundation for ongoing experimental work to evaluate cell death induced by 198AuNP which aims for the use of radioactive gold nanoparticles in cancer treatment. KW - AuNP KW - Beta decay KW - Beta particle KW - Brachytherapy KW - Cancer treatment KW - Nanoparticles KW - Nanoparticle KW - DNA KW - DNA damage KW - Dosimetry KW - Energy deposit KW - Gamma ray KW - Geant4 KW - Geant4-DNA KW - Gold Nanoparticles KW - LEE KW - Low energy electrons KW - MCS KW - Microdosimetry KW - Monte-Carlo simulation KW - NP KW - Synthesis KW - TEM KW - OH radicals KW - Particle scattering KW - Radiation damage KW - Radiationtherapy KW - Radioactive decay KW - Radiolysis KW - Simulation KW - TOPAS KW - TOPAS-nbio PY - 2022 DO - https://doi.org/10.1007/s10967-022-08355-5 SN - 1588-2780 SP - 1 EP - 9 PB - Springer Nature AN - OPUS4-55132 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Hallier, Dorothea C. A1 - Smales, Glen Jacob A1 - Seitz, H. A1 - Hahn, Marc Benjamin T1 - Bio-SAXS of single-stranded DNA-binding proteins: Radiation protection by the compatible solute ectoine N2 - Small-angle X-ray scattering (SAXS) can be used for structural determination of biological macromolecules and polymers in their native states (e.g. liquid phase). This means that the structural changes of (bio-)polymers, such as proteins and DNA, can be monitored in situ to understand their sensitivity to changes in chemical environments. In an attempt to improve the reliability of such experiments, the reduction of radiation damage occurring from exposure to X-rays is required. One such method, is to use scavenger molecules to protect macromolecules against radicals produced during radiation exposure, such as reactive oxygen species (ROS). In this study we investigate the feasibility of applying the compatible solute, osmolyte and radiation protector Ectoine (THP(B)), as a scavenger molecule during SAXS measurements of the single-stranded DNA-binding protein Gene-V Protein (G5P/GVP). In this case, we monitor the radiation induced changes of G5P during bio-SAXS measurments and the resulting microscopic energy-damage relation was determined from microdosimetric calculations by Monte-Carlo based particle scattering simulations with TOPAS/Geant4 and a custom target-model. This resulted in a median-lethal energy deposit of pure G5P at 4 mg mL−1 of E1/2 = 7 ± 5 eV, whereas a threefold increase of energy-deposit was needed under the presence of Ectoine to reach the same level of damage. This indicates that Ectoine increases the possible exposure time before radiation-damage to G5P is observed. Furthermore, the dominant type of damage shifted from aggregation in pure solutions towards a fragmentation for solutions containing Ectoine as a cosolute. These results are interpreted in terms of indirect radiation damage by reactive secondary species, as well as post-irradiation effects, related to preferential-exclusion of the cosolute from the protein surface. Hence, Ectoine is shown to provide a non-disturbing way to improve structure-determination of proteins via bio-SAXS in future studies. KW - BioSAXS KW - Bio-SAXS KW - Cosolute KW - Ectoine KW - G5P KW - GVP KW - Radiation damage KW - Radical Scavenger KW - Single-stranded DNA-binding proteins KW - X-ray scattering KW - DNA KW - ssDNA KW - Protein KW - SAXS KW - Small-angle xray scattering KW - McSAS3 KW - Dosimetry KW - Microdosimetry KW - Geant4 KW - Geant4-DNA KW - Topas KW - Topas-MC KW - Monte-Carlo simulations KW - Particle scattering simulations KW - Topas-nBio KW - OH Radical KW - OH radical scavenger KW - LEE KW - Ionizing radiation damage KW - Protein unfolding KW - Ectoin PY - 2023 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-568909 DO - https://doi.org/10.1039/d2cp05053f SN - 1463-9076 SN - 1463-9084 VL - 25 IS - 7 SP - 5372 EP - 5382 PB - Royal Society of Chemistry CY - Cambridge AN - OPUS4-56890 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Hallier, Dorothea C. A1 - Smales, Glen Jacob A1 - Seitz, H. A1 - Hahn, Marc Benjamin T1 - Inside back cover for the article "Bio-SAXS of single-stranded DNA-binding proteins: Radiation protection by the compatible solute ectoine" N2 - Showcasing research from the Federal Institute for Material Research and Testing Berlin and Fraunhofer Institute for Celltherapy and Immunology Branch Bioanalytics and Bioprocesses Potsdam. Bio-SAXS of single-stranded DNA-binding proteins: Radiation protection by the compatible solute ectoine. We aimed to increase the possible undisturbed exposure time during bio-SAXS measurements of single-stranded DNA-binding proteins. Therefore small angle X-ray scattering was performed on Gene-V Protein (G5P/GVP), which is involved in DNA repair processes. To achieve this, irradiations were performed in presence and absence of the hydroxyl-radical scavenger and osmolyte Ectoine, which showed efficient radiation protection and prevented protein aggregation, thus allows for a non-disturbing way to improve structure-determination of biomolecules. KW - Bio-SAXS KW - BioSAXS KW - Cosolute KW - DNA KW - Dosimetry KW - Ectoin KW - Ectoine KW - G5P KW - GVP KW - Geant4 KW - Geant4-DNA KW - Ionizing radiation damage KW - LEE KW - McSAS3 KW - Microdosimetry KW - Monte-Carlo simulations KW - OH Radical KW - OH radical scavenger KW - Protein KW - Protein unfolding KW - Radiation damage KW - Radical Scavenger KW - SAXS KW - Single-stranded DNA-binding proteins KW - Small-angle xray scattering KW - Topas-MC KW - Topas-nBio KW - TopasMC KW - X-ray scattering KW - Particle scatterin simulations KW - ssDNA PY - 2023 DO - https://doi.org/10.1039/D3CP90056H SN - 1463-9076 SN - 1463-9084 VL - 25 IS - 7 SP - 5889 PB - Royal Society of Chemistry CY - Cambridge AN - OPUS4-57006 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -