A multiscale modelling approach has been established for the interaction of charged particles with biologically relevant condensed-phase materials, including liquid water (the main constituent of biological tissue), DNA/RNA building blocks, as well as heavy metals and their oxides typically used in radioenhancing NPs. The methodology is based on the combination of (i) the semiempirical dielectric formalism (providing reliable charged particle cross sections in condensed matter in a wide energy range), (ii) time-dependent density functional theory (TDDFT, offering a precise calculation of the electronic excitation spectra of complex materials over a wide range of energy and momentum transfers), and (iii) the implementation of the obtained cross sections into ab initio-informed Monte Carlo simulations.
Regarding aspect (i), the dielectric formalism (already well established for ion impact) has been extended for its use for very low energy electrons. The implementation of appropriate corrections has allowed the calculation of reliable electronic excitation and ionisation cross sections for electrons, from the high energies characteristic of ion-induced delta-electrons down to the electronic excitation threshold, the most important energy range in hadron-therapy. The very good comparison with a wide collection of experimental data for water and DNA/RNA building blocks demonstrates the reliability of this method.
With respect to aspect (ii), a TDDFT methodology has been set up for the reliable calculation of the electronic excitation spectra of different complex condensed-phase materials, including liquid water and the metals and metal oxides typically used for radioenhancing NPs. For liquid water, the ab initio calculated excitation spectrum perfectly reproduced the most recent set of experimental data. Its use within the dielectric formalism has improved its accuracy, producing cross sections which, for very low energy electrons (below 50 eV), yield an even better agreement with the experiments. For inorganic materials commonly used in NPs, such as gold or cerium oxide, the TDDFT methodology also provides results in very good agreement with experiments.
As per aspect (iii), the cross sections have been implemented in the Monte Carlo code SEED (Secondary Electron Energy Deposition) in order to study the electron production and propagation in situations of relevance for the project objectives. On the one hand, the energy and angular distributions of secondary electrons produced by carbon ions (one of the most promising projectiles currently used in hadron-therapy) in liquid water have been obtained in a wide range of ion energies (covering the plateau and maximum of the Bragg peak, but also conditions typical of cosmic radiation affecting manned space travel). The ions' track-structure produced by the electrons have been studied in detail, obtaining nanodosimetric information relevant for assessing the biological effects of radiation, namely, the clustering of damaging events in volumes similar to those of DNA molecules. The simulations reproduced very well the experimentally available nanodosimetric data on ionisation clusters, and gave further insights into the role of other physical mechanisms on the production of clustered biodamage on the nanoscale, difficult or impossible to obtain experimentally. On the other hand, the simulation of the electron propagation in materials forming radioenhancing NPs, such as cerium oxides, has also been performed, delivering detailed information on both their electronic excitation spectra and how they affect in turn the electron propagation.
Three peer-reviewed articles have been published in internationally recognised journals, two of them highlighted in the journal's back cover, one being included in the prestigious "PCCP 2021 Hot Articles" list. Two more manuscripts have been submitted for publication and several are under preparation. The work has been communicated in 7 international conferences. A complete outreach plan has been developed by means of a dedicated website, a social media account, and through activities for the general public such as the European Researchers' Night.
