A computational protocol for construction and atomistic-level characterization of coated metal NPs in explicit molecular media was designed, based on the advanced software packages MBN Explorer and MBN Studio, developed at the host institution. The protocol was applied to study nanometer-sized gold NPs coated with poly(ethylene glycol) (PEG), a commonly used coating material in biomedical applications, and galactose molecules. The dependence of structural properties of the NPs on the thickness and surface density of the coatings was elaborated.
It was demonstrated that the structure of the coating layer for the NPs solvated in water depends strongly on the surface density of ligands. In the case of PEG, at low surface densities of ligands, the coating represents a mixture of different conformation states, whereas elongated “brush”-like structures are formed predominantly at higher densities of ligands. Molecular dynamics simulations revealed a 10-30% increase of water density over the ambient value at a few Angstroms distance from the gold surface. This effect occurs due to the strong van der Waals interaction between gold atoms of the metal core and oxygen atoms of water molecules. A denser water layer in close proximity to the metal surface may enhance hydroxyl radicals production due to low-energy electrons (LEEs) emitted from metallic NPs. Therefore, metal NPs with low-density coatings may possess enhanced radiosensitising properties than their more densely coated counterparts. This methodology enables systematic exploration of different parameters (such as size, composition and density) of the metal core, organic coatings, and the molecular environment on the atomistic level, which remains a formidable and costly experimental task.
Transport of LEEs emitted from the metal core of ion-irradiated coated gold NPs was analyzed by means of the diffusion equation-based approach. The diffusion coefficients of electrons propagating through the coatings were determined as a function of electron kinetic energy through elastic mean free paths. Attenuation of electrons experiencing inelastic collisions was accounted for by introducing the characteristic lifetimes of electrons of a given energy, defined through the inelastic mean free paths. This methodology enabled the evaluation of the number density of secondary electrons released into the medium after ionization and the diffusion through the coating as a function of radial distance and time.
Computational modelling of ion-irradiation induced processes involving radiosensitising metal NPs implies the use of molecular dynamics simulations with the reactive rCHARMM force field and Irradiation-Driven Molecular Dynamics (IDMD) - the advanced computational methodology for the molecular-level description of chemical and irradiation-driven transformations. In the course of Radio-NP, these methods were utilized and thoroughly validated for several research problems closely linked to the topic of the project. The rCHARMM force field was used to study irradiation-induced chemistry transformations in solvated biomolecular systems irradiated with ions. The focus was made on elucidating radiation damage effects due to the nanoscale shock waves induced by the ions propagating through a biomolecular medium. The most representative case was selected for this study, namely ion-irradiation induced damage and fragmentation of the DNA molecule. The IDMD method was exploited for simulating irradiation-driven chemistry processes involving metal nanostructures embedded in organic environments and placed on a substrate. In such systems the interaction of metal parts with organic ligands and the irradiation-induced chemistry governed by secondary LEEs are similar to the case of coated metal NPs placed in biomolecular media. Using these methodologies radiation-induced chemical transformations in the vicinity of the coated gold NPs placed in the water medium have been investigated.
The conducted research has resulted so far in 4 peer-reviewed journal publications and 3 manuscripts submitted for publication. The obtained results and the underlying methodology have been disseminated through participation in a major international conference, a training school for young researchers, and several workshops and scientific meetings.
