Two-dimensional nanomaterials, specifically MoS2 nanosheets, are at the forefront of the current biomedical-related nanoscience research due to their great potential in biosensing, drug delivery, and biocatalysis. Their unique physicochemical properties and biocompatibility make MoS2 a prospective platform for anticancer drug delivery and photothermal therapy of cancers. Among physical methods actively used for the nanomaterial characterization, the modern mass spectrometry techniques, in particular the laser desorption/ionization (LDI) method, demonstrate high efficiency and informativeness. In this study, we examine intermolecular interactions between the components of nanocomposites of the MoS2 nanoparticles with anticancer thioderivatives of purine nucleobases, 6-thiopurine (TP) and 2-thioadenine (TA), using LDI mass spectrometry and theoretical quantum-chemical modeling. These interactions are important to the properties associated with drug delivery. The results of the LDI mass spectrometric examination of the nanocomposites show that a certain amount of the drug molecules retain their molecular integrity within the nanocomposite, which is a prerequisite for the therapeutic efficacy of the anticancer nanosystems studied in this work. At the same time, a detailed analysis of the LDI mass spectra obtained in the study allows us to determine that some molecules of TP and TA undergo chemical transformations, including oxidation, in the presence of catalytically active MoS2 particles. Ab initio DFT modeling (M06-2X) is employed to determine the structural configurations and binding energies of the nanocomplexes of MoS2 with the studied drug molecules. The results of the calculations show that TA and TP molecules can form stable stacking complexes with the surface of the MoS2 nanosheets, as well as covalent complexes with the edges of the sheets. The present study shows that the chemical alteration of the anticancer thioderivatives induced by MoS2 may modulate the therapeutic activity of thiol-based drugs. This effect can be important for future biomedical applications of nanocomposites of MoS2 with TP and TA.
Pashynska et al. (Thu,) studied this question.