Probing the Influence of Hydrophobicity of Modified\nGold Nanoparticles in Modulating the Lipid Surface Behavior Using\nVibrational Sum Frequency Generation Spectroscopy

A deep understanding of how the surface\nmodifications of nanoparticles\nimpact their interactions with cell membranes is vital for advancing\nsafe and effective biomedical applications. Among the pivotal factors\ngoverning these interactions, the hydrophobicity of nanoparticles\nplays a crucial role, predominantly driven by the hydrophobic interactions\nwith the cell membrane. Herein, we study the influence of the hydrophobic\nalkyl chain length of thiol-capped gold nanoparticles (GNPs) on lipid\nsurfaces with the help of vibrational sum frequency generation spectroscopy.\nWe have utilized the zwitterionic 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine (DPPC) lipid monolayer as a representative\nmodel of cell membranes on the water surface. Our findings revealed\nthat GNPs capped with the thiol ligand having a shorter alkyl chain\nsuch as heptanethiol (HT, C<sub>7</sub>) show minimal changes in the\nC–H stretching vibrations while interacting with the lipid\nmonolayer. These observations could be attributed to the perturbation\nof the lipid chain due to hydrophobic–hydrophobic interactions\nbetween the alkyl chain of thiol-capped GNPs and the hydrophobic group\nof the lipid membrane or simply by the adsorption of GNPs at the interface\nwithout disrupting the monolayer structure. However, with increasing\nthe chain length of thiol-capped GNPs from decanethiol (DDT, C<sub>10</sub>) to octadecanethiol (ODT, C<sub>18</sub>), the extent of\nspectral change in the C–H stretching vibration is increased.\nThe controlled experiment performed with the deuterated lipids conforms\nthat the changes observed in the C–H stretching vibration after\nadding HT (C<sub>7</sub>) GNPs are only because of their presence\nin the surface without altering the monolayer structure. However,\nin the case of DT (C<sub>10</sub>) and DDT (C<sub>12</sub>) GNPs,\nthe strong hydrophobic interactions between the monolayer and the\nalkyl chain of the thiol-capped GNPs result in the increased orientational\norder of the monolayer. Moreover, in the case of ODT (C<sub>18</sub>) GNPs, the very long alkyl chain induces pronounced perturbations\nin the monolayer structure with net disordering of the monolayer.\nThese observations are further supported by the spectral changes observed\nin the O–H vibration of the interfacial water molecules. Our\nfindings reveal the crucial role of the hydrophobic nature of GNPs\nin influencing the interface. Understanding these effects is crucial\nfor drug delivery applications and improving the stability and effectiveness\nof lipid-based systems.