Probing the Influence of Hydrophobicity of Modified Gold Nanoparticles in Modulating the Lipid Surface Behavior Using Vibrational Sum Frequency Generation Spectroscopy

A deep understanding of how the surface modifications of nanoparticles impact their interactions with cell membranes is vital for advancing safe and effective biomedical applications. Among the pivotal factors governing these interactions, the hydrophobicity of nanoparticles plays a crucial role, predominantly driven by the hydrophobic interactions with the cell membrane. Herein, we study the influence of the hydrophobic alkyl chain length of thiol-capped gold nanoparticles (GNPs) on lipid surfaces with the help of vibrational sum frequency generation spectroscopy. We have utilized the zwitterionic 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid monolayer as a representative model of cell membranes on the water surface. Our findings revealed that GNPs capped with the thiol ligand having a shorter alkyl chain such as heptanethiol (HT, C₇) show minimal changes in the C–H stretching vibrations while interacting with the lipid monolayer. These observations could be attributed to the perturbation of the lipid chain due to hydrophobic–hydrophobic interactions between the alkyl chain of thiol-capped GNPs and the hydrophobic group of the lipid membrane or simply by the adsorption of GNPs at the interface without disrupting the monolayer structure. However, with increasing the chain length of thiol-capped GNPs from decanethiol (DDT, C₁₀) to octadecanethiol (ODT, C₁₈), the extent of spectral change in the C–H stretching vibration is increased. The controlled experiment performed with the deuterated lipids conforms that the changes observed in the C–H stretching vibration after adding HT (C₇) GNPs are only because of their presence in the surface without altering the monolayer structure. However, in the case of DT (C₁₀) and DDT (C₁₂) GNPs, the strong hydrophobic interactions between the monolayer and the alkyl chain of the thiol-capped GNPs result in the increased orientational order of the monolayer. Moreover, in the case of ODT (C₁₈) GNPs, the very long alkyl chain induces pronounced perturbations in the monolayer structure with net disordering of the monolayer. These observations are further supported by the spectral changes observed in the O–H vibration of the interfacial water molecules. Our findings reveal the crucial role of the hydrophobic nature of GNPs in influencing the interface. Understanding these effects is crucial for drug delivery applications and improving the stability and effectiveness of lipid-based systems.