Molecular dynamics of hydrophobic transport using monolayer-protected nanoparticles

Proteins such as serum albumin contain apolar pockets in their three-dimensional structure that facilitate the transport of hydrophobic small molecules in biological settings. Nanoscale carriers that can similarly solubilize therapeutic compounds without requiring chemical modification have immense value as drug delivery systems. Here, we use molecular dynamics simulations to demonstrate that gold nanoparticles functionalized with alkanethiol ligands can passively encapsulate hydrophobic molecules. We focus on the encapsulation of long-chain fatty acids and study the thermodynamics and kinetics of incorporation into the nanoparticle's surface monolayer as a function of chain length and unsaturation. We also characterize the structure of the nanoparticle and organization of the encapsulated molecules as a function of loading density and demonstrate that loaded nanoparticles release their cargo into lipid membranes upon contact with fluctuations such as lipid tail protrusions. These observations suggest the possibility of designing nanomaterials that can function as synthetic mimics of transport proteins and have applications in solubilizing apolar pharmaceutical compounds in the aqueous environment of biological systems.