Hexagonal boron nitride nanosheet as novel drug delivery system for anticancer drugs: Insights from DFT calculations and molecular dynamics simulations.

Density functional theory (DFT) calculations and molecular dynamic (MD) simulations were accomplished to comprehend the nature of the interactions between 5-fluorouracil (FU)/6-mercaptopurine (MP)/6-thioguanine (TG) anticancer drugs and hexagonal boron nitride (BN) nanosheet as a drug delivery system. It is found from the calculations that the adsorption process of drug molecules on the BN nanosheet is exothermic and occurs spontaneously. The polarity for the drug loaded complexes, offers the possibility of improving the condition of solubility, which is favorable for drug delivery in biological media. Orbital energy and density of state (DOS) calculations show that HOMO-LUMO energy gap of BN nanosheet decreases upon the adsorption of drug molecules. The quantum molecular descriptors show that the absorption of drugs on BN nanosheet increases the chemical reactivity. The results of the energy decomposition analysis (EDA) indicated that the dispersion interaction plays a predominant role in the stabilization of the drug-BN complexes. The intermolecular interactions were also investigated by the noncovalent interaction (NCI) and quantum theory of atoms in molecules (QTAIM) analyses. The MD results showed that the average of the interaction energy values in acidic conditions are lower (absolute values) than corresponding values obtained at neutral pH, which indicated the drug could be released within the target cancer cells. These findings contribute to the development of drug delivery systems based on BN nanosheet for delivery of anticancer drugs.