Molecular Dynamics Characterization of Radiosensitizing Coated Gold Nanoparticles in Aqueous Environment

Functionalized metal nanoparticles (NPs) havebeen proposed as promising radiosensitizing agents for moreefficient radiotherapy treatment using photons and ion beams.Radiosensitizing properties of NPs may depend on many differentparameters (such as size, composition, and density) of the metalcore, the organic coatings, and the molecular environment. Asystematic exploration of each of these parameters on the atomisticlevel remains a formidable and costly experimental task, but it canbe addressed by means of advanced computational modeling. Thispaper describes a detailed computational procedure for con-struction and atomistic-level characterization of radiosensitizingmetal NPs in explicit molecular media. The procedure is general and is extensible to many different combinations of the core,coating, and environment. As an illustrative and experimentally relevant case study, we consider nanometer-sized gold NPs coatedwith thiol-poly(ethylene glycol)-amine molecules of different length and surface density and solvated in water at ambientconditions. The radial distribution of different atoms in the coatings as well as distribution and structural properties of water aroundthe coated NPs are analyzed and linked to radiosensitizing properties of the NPs. It is revealed that the structure of the coating layeron the solvated NPs depends strongly on the surface density of ligands. At surface densities below similar to 3 molecules/nm2the coatingrepresents a mixture of different conformation states, whereas elongatedbrush-like structures are formed at higher densities ofligands. The water content in denser coatings is significantly lower at distances from 1 nm up to 3 nm from the gold surfacedepending on the length of ligand molecules. Such dense and thick coatings may suppress the production of hydroxyl radicals bylow-energy electrons emitted from the metal NPs and thus diminish their radiosensitizing properties. The presented computationalframework provides precise information for a quantitative atomistic-level description of the structural properties of coated metal NPsin biologically relevant environments and so may form a basis for future developments to achieve a more realistic description ofirradiation-driven chemistry effects in the vicinity of coated metal NPs.

Automated summary

Functionalized metal nanoparticles have been proposed as radiosensitizing agents in radiotherapy. This study explores the effects of different parameters on the radiosensitizing properties of metal nanoparticles using computational modeling. It focuses on the coating structure of gold nanoparticles and reveals that dense and thick coatings may diminish their radiosensitizing properties.