Radiotherapy is currently used in around 50% of cancer treatments and relies on the deposition of energy directly into tumour tissue. Although it is generally effective, some of the deposited energy can adversely affect healthy tissue outside the tumour volume, especially in the case of photon radiation (gamma and X-rays). Improved radiotherapy outcomes can be achieved by employing ion beams due to the characteristic energy deposition curve which culminates in a localised, high radiation dose (in form of a Bragg peak). In addition to ion radiotherapy, novel sensitisers, such as nanoparticles, have shown to locally increase the damaging effect of both photon and ion radiation, when both are applied to the tumour area. Amongst the available nanoparticle systems, gold nanoparticles have become particularly popular due to several advantages: biocompatibility, well-established methods for synthesis in a wide range of sizes, and the possibility of coating of their surface with a large number of different molecules to provide partial control of, for example, surface charge or interaction with serum proteins. This gives a full range of options for design parameter combinations, in which the optimal choice is not always clear, partially due to a lack of understanding of many processes that take place upon irradiation of such complicated systems. In this review, we summarise the mechanisms of action of radiation therapy with photons and ions in the presence and absence of nanoparticles, as well as the influence of some of the core and coating design parameters of nanoparticles on their radiosensitisation capabilities.

The transport of low-energy electrons through the coating of a radiosensitizing metallic nanoparticle under fast ion irradiation is analyzed theoretically and numerically. As a case study, we consider a poly(ethylene glycol)-coated gold nanoparticle of diameter 1.6 nm excited by a carbon ion in the Bragg peak region in water as well as by more energetic carbon ions. The diffusion equation for low-energy electrons emitted from a finite-size spherical source representing the surface of the metal core is solved to obtain the electron number density as a function of radial distance and time. Information on the atomistic structure and composition of the coating is obtained from molecular dynamics simulations performed with the MBN Explorer software package. Two mechanisms of low-energy electron production by the metallic core are considered: the relaxation of plasmon excitations and collective excitations of valence d electrons in individual atoms of gold. Diffusion coefficients and characteristic lifetimes of electrons propagating in gold, water, and poly(ethylene glycol) are obtained from relativistic partial wave analysis and the dielectric formalism, respectively. On this basis, the number of electrons released through the organic coating into the surrounding aqueous medium and the number of hydroxyl radicals produced are evaluated. The largest increase of the radical yield due to low-energy electrons is observed when the nanoparticle is excited by an ion with energy significantly exceeding that in the Bragg peak region. It is also shown that the water content of the coating, especially near the surface of the metal core, is crucial for the production of hydroxyl radicals. a

Abstract. Gold nanoparticles (AuNPs) have been shown to possess properties beneficial for the treatment of cancerous tumors by acting as radiosensitizers for both photon and ion radiation. Blood circulation time is usually increased by coating the AuNPs with poly(ethylene glycol) (PEG) ligands. The effectiveness of the PEG coating, however, depends on both the ligand surface density and length of the PEG molecules, making it important to understand the structure of the coating. In this paper the thickness, ligand surface density, and density of the PEG coating is studied with classical molecular dynamics using the software package MBN Explorer. AuNPs consisting of 135 atoms (approximately 1.4 nm diameter) in a water medium have been studied with the number of PEG ligands varying between 32 and 60. We find that the thickness of the coating is only weakly dependent on the surface ligand density and that the degree of water penetration is increased when there is a smaller number of attached ligands.