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Accessing radiation damage to biomolecules on the nanoscale by particle-scattering simulations
(2023)
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.
Different approaches have been proposed to treat cancer cells using gold nanoparticles (AuNPs) in combination with radiation ranging from infrared lasers to high-energy ion beams. Here we study the decomposition of the DNA/RNA nucleobases thymine (T) and uracil (U) and the well-known radiosensitizer 5-bromouracil (BrU) in close vicinity to AuNPs, which are irradiated with a nanosecond pulsed laser (532 nm) matching the surface plasmon resonance of the
AuNPs. The induced damage of nucleobases is analyzed by UV−vis Absorption spectroscopy and surface-enhanced Raman scattering (SERS). A clear DNA damage is observed upon laser irradiation. SERS spectra indicate the fragmentation of the aromatic ring system of T and U as the dominant form of damage, whereas with BrU mainly the cleavage of the Br−C bond and formation of Br− ions is observed. This is accompanied by a partial transformation of BrU into U. The observed damage is at least partly ascribed to the intermediate formation of lowenergy electrons from the laser-excited AuNPs and subsequent dissociative electron attachment to T, U, and BrU. These reactions represent basic DNA damage pathways occurring on the one hand in plasmon-assisted cancer therapy and on the other hand in conventional cancer radiation therapy using AuNPs as sensitizing agents.