Amino acid-modified graphene as a promising nanocarrier for anticancer drugs hydroxyurea and 6-thioguanine: DFT and MD investigations

This study investigates the potential of amino acid-modified graphene (AA-GR) as an effective nanocarrier for delivering two anticancer drugs: hydroxyurea (HU) and 6-thioguanine (TG). Using Density Functional Theory (DFT) and Molecular Dynamics (MD) simulations, the interactions between AA-modified graphene and the selected drugs were thoroughly investigated. Various amino acids—alanine, cysteine, glycine, tryptophan, and tyrosine—were anchored to the graphene surface, with tryptophan-modified graphene (Trp-GR) exhibiting the strongest drug binding. DFT calculations revealed that the adsorption of HU and TG onto AA-GR surfaces is exothermic and spontaneous, with Trp-GR displaying the highest adsorption energy (−31.83 kcal/mol) and the most favorable thermodynamic properties. The calculated Gibbs free energy (ΔG) values for both drugs were negative, confirming the stability of the complexes. MD simulations further demonstrated the stability and dynamic behavior of the drug–nanocarrier complexes in aqueous environments, highlighting the suitability of AA-GR as a potential drug delivery system. The results also show that Trp-GR can adsorb up to five TG molecules, with efficient and rapid drug desorption at physiological temperatures, making it an ideal candidate for controlled drug release. This work paves the way for the development of amino acid-modified graphene as a promising platform for targeted anticancer drug delivery.