Functionalized MoS₂ nanosheets as high-affinity nanocarriers for gemcitabine: a molecular simulation study

In this study, molecular dynamics (MD) simulations were employed to investigate the adsorption mechanisms of the chemotherapeutic drug gemcitabine (GEM) on pristine and functionalized molybdenum disulfide (MoS₂) nanosheets. The functionalization of MoS₂ was achieved by incorporating polyethyleneimine (PEI), polyethylene glycol (PEG), and cytosine-phosphate-guanine (CPG) groups, enhancing the material's drug adsorption capacity. Our simulations reveal that the MoS₂/CPG-PEI-PEG system exhibits a significantly higher affinity for GEM compared to pristine MoS₂, with interaction energies reaching -236 kJ/mol, driven primarily by van der Waals (vdW) interactions and electrostatic forces. Metadynamics simulations further confirm that the global minimum free energy for the functionalized system is approximately -237 kJ/mol, compared to -199 kJ/mol for pristine MoS₂. Radial distribution function (RDF) analysis and density profiles highlight stronger drug-substrate interactions and reduced solvent exposure in the functionalized system, which also exhibits lower drug mobility, suggesting more stable adsorption. These findings are supported by experimental data, demonstrating that functionalized MoS₂ nanosheets offer a promising platform for enhancing drug delivery systems. This work underscores the importance of surface functionalization in optimizing drug adsorption and stability, offering valuable insights for the development of more efficient nanomaterials in targeted drug delivery applications.