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

Area of Science:

• Materials Science
• Nanotechnology
• Computational Chemistry

Background:

• Molybdenum disulfide (MoS₂) nanosheets are explored for drug delivery applications.
• Surface functionalization is key to enhancing nanomaterial adsorption capacity.
• Gemcitabine (GEM) is a chemotherapeutic agent with potential for targeted delivery.

Purpose of the Study:

• To investigate gemcitabine (GEM) adsorption on pristine and functionalized molybdenum disulfide (MoS₂) nanosheets using molecular dynamics (MD) simulations.
• To evaluate the impact of polyethyleneimine (PEI), polyethylene glycol (PEG), and cytosine-phosphate-guanine (CPG) functionalization on MoS₂'s drug adsorption capabilities.
• To understand the adsorption mechanisms and stability of GEM on functionalized MoS₂ for potential drug delivery applications.

Main Methods:

• Molecular dynamics (MD) simulations were performed to model GEM adsorption on MoS₂.
• Metadynamics simulations were used to determine the global minimum free energy.
• Radial distribution function (RDF) analysis and density profiles were employed to assess drug-substrate interactions and solvent exposure.

Main Results:

• The MoS₂/CPG-PEI-PEG system demonstrated significantly higher GEM affinity (-236 kJ/mol) compared to pristine MoS₂.
• Functionalized MoS₂ exhibited a lower global minimum free energy (-237 kJ/mol) than pristine MoS₂ (-199 kJ/mol).
• Enhanced interactions, reduced solvent exposure, and lower drug mobility were observed for GEM on functionalized MoS₂, indicating more stable adsorption.

Conclusions:

• Surface functionalization of MoS₂ nanosheets with CPG-PEI-PEG substantially improves gemcitabine adsorption and stability.
• Functionalized MoS₂ offers a promising platform for developing advanced drug delivery systems.
• This study highlights the critical role of surface modification in optimizing nanomaterials for targeted drug delivery.