TY - JOUR A1 - Hahn, Marc Benjamin A1 - Zutta Villate, J. M. ED - Zutta Villate, J. M. T1 - Combined cell and nanoparticle models for TOPAS to study radiation dose enhancement in cell organelles 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. 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. 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 future experimental work which aims to obtain a mechanistic understanding of cell death induced by radioactive 198Au. KW - AuNP KW - Beta decay KW - Brachytherapy KW - Cancer treatment KW - DNA KW - DNA damage KW - Dosimetry KW - Energy deposit KW - Geant4 KW - Geant4-DNA KW - Gold Nanoparticles KW - LEE KW - MCS KW - Microdosimetry KW - Monte-Carlo simulation KW - NP KW - Ectoine KW - OH radicals KW - Radiation damage KW - Radiationtherapy KW - Radioactive decay KW - Simulation KW - Beta particle KW - Clustered nanoparticles KW - Gamma ray KW - Low energy electrons KW - Particle scattering KW - Radiolysis KW - Livermore model KW - Penelope model KW - TOPAS KW - TOPAS-nbio PY - 2021 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-523276 DO - https://doi.org/10.1038/s41598-021-85964-2 SN - 2045-2322 VL - 11 IS - 1 SP - 6721 PB - Springer Nature AN - OPUS4-52327 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - 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 - 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 - Hahn, Marc Benjamin A1 - Zutta Villate, Julian Mateo T1 - Radioactive gold nanoparticles for cancer treatment: Size and cluster dependent damage studied by Geant4 Monte-Carlo simulations N2 - Dose enhancement by gold nanoparticles (AuNP) was shown to increase the biological effectiveness of radiation damage in biomolecules and tissue. Most of the current studies focus on external beam therapy on combination with AuNP. Here we present a Monte-Carlo study (Geant4) to characterise radioactive AuNP. Radioactive ¹⁹⁸Au emits beta and gamma rays and is considered for applications with solid tumours. To effectively apply ¹⁹⁸AuNP their energy deposit characteristics have to be determined in terms of intrinsic and extrinsic properties e.g. AuNP diameter, AuNP density, and their clustering behaviour. After each decay process, the energy deposit, inelastic scattering events, kinetic energy spectrum of secondary particles within the AuNP themselves and in a spherical target volume of water up to 1 μm radius were determined. Simulations were performed for AuNP radii ranging from 2.5 nm to 20 nm radius, different cluster sizes and densities. The results show an increase of the energy deposit in the vicinity of the AuNP up to 150 nm. This effect nearly vanishes for distances up to one micron. For the case of AuNP clusters and the same activity, the enhancement of the energy deposit increases with the relative gold mass percentage and therefore can be adjusted by changing AuNP radius or clustering behaviour. KW - Gold Nanoparticles KW - AuNP KW - Radioactive decay KW - Beta decay KW - DNA KW - DNA damage KW - Radiation damage KW - MCS KW - Monte-Carlo simulation KW - Geant4 KW - Dosimetry KW - Microdosimetry KW - Cancer treatment KW - Radiationtherapy KW - Brachytherapy KW - OH radicals KW - LEE KW - low energy electrons KW - gamma ray KW - beta particle KW - radiolysis KW - clustered nanoparticles KW - NP KW - Simulation KW - particle scattering KW - Geant4-DNA KW - Energy deposit PY - 2019 DO - https://doi.org/10.1140/epjd/e2019-90707-x SN - 1434-6060 SN - 1434-6079 VL - 73 IS - 5 SP - 95, 1 EP - 7 PB - Springer CY - Berlin Heidelberg AN - OPUS4-47952 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - Radioactive gold nanoparticles for cancer treatment: Size and cluster dependent damage studied by Geant4 Monte-Carlo simulations N2 - Dose enhancement by gold nanoparticles (AuNP) was shown to increase the biological effectiveness of radiation damage in biomolecules and tissue. Most of the current studies focus on external beam therapy on combination with AuNP. Here we present a Monte-Carlo study (Geant4) to characterise radioactive AuNP. Radioactive ¹⁹⁸Au emits beta and gamma rays and is considered for applications with solid tumours. To effectively apply ¹⁹⁸AuNP their energy deposit characteristics have to be determined in terms of intrinsic and extrinsic properties e.g. AuNP diameter, AuNP density, and their clustering behaviour. After each decay process, the energy deposit, inelastic scattering events, kinetic energy spectrum of secondary particles within the AuNP themselves and in a spherical target volume of water up to 1 μm radius were determined. Simulations were performed for AuNP radii ranging from 2.5 nm to 20 nm radius, different cluster sizes and densities. The results show an increase of the energy deposit in the vicinity of the AuNP up to 150 nm. This effect nearly vanishes for distances up to one micron. For the case of AuNP clusters and the same activity, the enhancement of the energy deposit increases with the relative gold mass percentage and therefore can be adjusted by changing AuNP radius or clustering behaviour. T2 - EUROMAT 2019 CY - Stockholm, Sweden DA - 01.09.2019 KW - DNA KW - Dosimetry KW - Microdosimetry KW - Geant4 KW - MCS KW - Nanoparticle KW - AuNP KW - Gold Nanoparticle KW - low energy electrons KW - LEE KW - OH radicals KW - particle scattering KW - Radiationtherapy KW - Radioactive decay KW - Monte-Carlo simulation KW - Energy deposit KW - DNA damage PY - 2019 AN - OPUS4-48763 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Hahn, Marc Benjamin A1 - Smales, Glen Jacob A1 - Seitz, H. A1 - Solomun, Tihomir A1 - Sturm, Heinz T1 - Ectoine interaction with DNA: Influence on ultraviolet radiation damage N2 - Ectoine is a small zwitterionic osmolyte and compatible solute, which does not interfere with cell metabolism even at molar concentrations. Plasmid DNA (pUC19) was irradiated with ultraviolet radiation (UV-C at 266 nm) under quasi physiological conditions (PBS) and in pure water in the presence and absence of ectoine (THP(B)) and hydroxyectoine (THP(A)). Different types of UV induced DNA damage were analysed: DNA single-strand breaks (SSBs), abasic sites and cyclobutane pyrimidine dimers (CPDs). A complex interplay between these factors was observed with respect to the nature and occurrence of DNA damage with 266 nm photons. In PBS, the cosolutes showed efficient protection against base damage, whilst in pure water, a dramatic shift from SSB damage to base damage was observed when cosolutes were added. To test whether these effects are caused by ectoine binding to DNA, further experiments were conducted: small-angle X-ray scattering (SAXS), surface-plasmon resonance (SPR) measurements and Raman spectroscopy. The results show, for the first time, a close interaction between ectoine and DNA. This is in stark contrast to the assumption made by preferential exclusion models, which are often used to interpret the behaviour of compatible solutes within cells and with biomolecules. It is tentatively proposed that the alterations of UV damage to DNA are attributed to ectoine influence on nucleobases through the direct interaction between ectoine and DNA. KW - Ectoine KW - DNA KW - Radiation damage KW - Radiation protection KW - SSB KW - DNA damage KW - DNA protection KW - Compatible solute KW - Zwitterion KW - Hydroxyectoine KW - Salt KW - PBS KW - UV absorption KW - DNA strand-break KW - DNA base damage KW - Ectoine UV absorption KW - Ectoine DNA protection KW - Excited states KW - UV irradiation KW - UV-A KW - UV-B KW - UV-C KW - 266nm KW - UV photons KW - Ectoine-DNA binding KW - Raman spectroscopy KW - UV-Vis KW - Radical scavenger KW - OH scavenger KW - Hydroxyl radicals KW - CPD KW - Abasic site KW - Agarose gel electrophorese KW - SYBR gold KW - DNA melting temperature KW - Counterions KW - Preferential exclusion KW - Cancer KW - Therapy KW - UV protection KW - Sunscreen PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-505772 DO - https://doi.org/10.1039/d0cp00092b SN - 1463-9076 SN - 1463-9084 VL - 22 IS - 13 SP - 6984 EP - 6992 PB - Royal Society of Chemistry CY - Cambridge AN - OPUS4-50577 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Hahn, Marc Benjamin T1 - Combination of Monte-Carlo simulations and experimental results to determine the microscopic energy depoit at DNA N2 - The quantification of radiation induced damage to DNA in aqueous en- vironment is of fundamental interest for dosimetry and its application in radiation-therapy and protection. We present a combined experi- mental and simulational approach to quantify and compare radiation induced damage to biomolecules in liquid environment for a wide range of primary radiation sources e. g. photons, electrons or ions and tar- gets, such as DNA, proteins or cells.[1] To show its viability, we will apply this method to an experimentally challenging systems, the di- rect irradiation of plasmid DNA (pUC19) in water with electrons as primary particles. Here we combine Geant4 electron-scattering simula- tions with calculations concerning the diffusion and convection induced movement of the biomolecules, within a coarse-grained model of the irradiated liquid. Additionally a microscopic target model for the plas- mid DNA based on the relation of lineal energy and radiation quality is used to calculate the effective target volume. T2 - DPG-Frühjahrstagung der Sektion Kondensierte Materie gemeinsam mit der EPS CY - Berlin, Germany DA - 11.03.2018 KW - DNA KW - Radiation damage KW - Dosimetry KW - Microdosimetry KW - Low energy electrons KW - Hydroxyl radicals KW - Monte-Carlo simulation KW - Geant4 KW - Electron scattering KW - Target volume KW - DNA damage KW - DNA radiation damage PY - 2018 AN - OPUS4-44565 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -