Hydrophobic Nanoparticles Modify the Thermal Release Behavior of Liposomes

Understanding the effect of embedded nanoparticles on the characteristics and behavior of lipid bilayers is critical to the development of lipid–nanoparticle assemblies (LNAs) for biomedical applications. In this work we investigate the effect of hydrophobic nanoparticle size and concentration on liposomal thermal release behavior. Decorated LNAs (D-LNAs) were formed by embedding 2 nm (GNP2) and 4 nm (GNP4) dodecanethiol-capped gold nanoparticles into DPPC liposomes at lipid to nanoparticle ratios (L:N) of 25,000:1, 10,000:1, and 5,000:1. D-LNA structure was investigated by cryogenic transmission electron microscopy, and lipid bilayer permeability and phase behavior were investigated based on the leakage of a model drug, carboxyfluorescein, and by differential scanning calorimetry, respectively. The presence of bilayer nanoparticles caused changes in the lipid bilayer release and phase behavior compared to pure lipid controls at very low nanoparticle to bilayer volume fractions (0.3%–4.6%). Arrhenius plots of the thermal leakage show that GNP2 led to greater increases in the leakage energy barrier compared to GNP4, consistent with GNP4 causing greater bilayer disruption due to their size relative to the bilayer thickness. Embedding hydrophobic nanoparticles as permeability modifiers is a unique approach to controlling liposomal leakage based on nanoparticle size and concentration.