Computational Modelling of Radiosensitising Properties of Nanoparticles

Metal nanoparticles (NPs) are currently under intense investigation due to their potential application in radiotherapy treatment of cancerous tumors by acting as radiosensitizing agents which may potentially lead to a reduction of side-effects caused by radiotherapy. This theses presents a framework to accurately explore a number of important parameters of coated NPs using computational and theoretical methods which may be applied to any coated NP system. The detailed structure of poly(ethylene glycol) (PEG)-coated gold nanoparticles (AuNPs) was studied using atomistic classical molecular dynamics simulations. By varying the number of attached PEG molecules it was demonstrated that the thickness of the coating, and therefore the size of the overall NP, was independent of the coating molecule surface density. On the other hand, the water content of the coating was observed to decrease with increased coating surface density. In particular, it was found that the region immediately outside the NP core was devoid of water for high coating densities. The energetics of the coating formation was investigated by calculating the free energy change associated with the binding of a PEG molecule to a gold surface. The binding was demonstrated to be energetically favourable with a dominating contribution coming from a decrease in potential energy associated with the binding. This methodology may be be extended to provide estimates for the lifetime on NP coatings in vivo where they have been shown to degraded by exchange with biological proteins post administration. The transport of low-energy secondary electrons emitted by carbon ion-irradiated AuNP was calculated as a diffusion process and the radical production, due to inelastic collisions of the electrons inside the coating medium, was quantified. By varying the ion energy and coating water content we demonstrated that the presence of water near NP surface is crucial in order to achieve radical production enhancement compared to pure water

Nanoparticles for Cancer Therapy

More than 50% of all cancer patients receive radiotherapy which largely means X-ray therapy. X-rays kill cells by the deposition of energy (the “dose”) into the cells, but unfortunately these X-rays also damage healthy cells. Furthermore, radiation is introduced from many angles to increase the dose on the tumor leading to irradiation of much more healthy tissue than strictly necessary - this can be detrimental, especially for brain tumors (see image). Therefore what is needed is a new therapy that allows more targeted application of the radiation to reduce damage to healthy cells

Modeling of nanoparticle coatings for medical applications

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

Transport of secondary electrons through coatings of ion-irradiated metallic nanoparticles

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.Comment: a contribution to the Special Issue "Atomic Cluster Collisions" of the European Physical Journal