Structural and Thermal Analysis of Lipid Vesicles Encapsulating Hydrophobic Gold Nanoparticles

Abstract

The structure and stability of hybrid lipid vesicles containing bilayer-encapsulated hydrophobic nanoparticles is dependent upon lipid phase behavior. By embedding stearylamine-stabilized gold nanoparticles in dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylglycerol vesicles, we show that encapsulation at lipid to nanoparticle ratios from 10,000:1 to 5000:1 leads to bilayer thickening and hydrophobic mismatch, favoring nanoparticle inclusion in gel phase vesicles. High loadings lead to large increases in the gel to fluid melting temperature upon heating and significant hysteresis on cooling, which cannot be attributed solely to excess free ligand. This behavior is due to a cooperative effect of excess free SA ligand and nanoparticle embedment. Nanoparticle clustering was observed during lipid melting and could be reversed upon lipid freezing owing to lateral capillary forces within the bilayer. The impact of nanoparticle embedment on vesicle structure and properties at such low concentrations is reminiscent of hydrophobic proteins, suggesting that the underlying lipid biophysics between proteins and nanoparticle are similar and may provide a predictive design tool for therapeutic applications.

General and programmable synthesis of hybrid liposome/metal nanoparticles

“…In addition, removal of free metal nanoparticles (that is, metal nanoparticles that are not encapsulated) and free liposomes (that is, liposomes that do not contain metal nanoparticles) must be done carefully through additional separations ( 25 – 27 ). On the other hand, metal nanoparticles can also be embedded between lipid bilayers or, alternatively, can be attached to the outer liposome surface through delicate control of their surface chemistry ( 21 , 23 , 28 – 30 ). However, for both methods, the metal nanoparticles should be small enough to produce a stable hybrid structure without degrading the structural integrity of the lipid bilayer.…”

Nanoparticle-triggered release from lipid membrane vesicles

“…A change in lipid ordering should also affect the phase transition, but no significant change in the T m of liposome bilayers was observed after incorporating palmityl-nitroDOPA stabilized 5 nm core diameter iron oxide nanoparticles in the liposome membranes [21]. Relatively disperse sterylamine coated nanoparticles in LUVs were also reported by Bothun et al [24]. They further reported effects on lipid organization and T m that was depended on nanoparticlelipid ratio.…”

“…Magnetically responsive nanoparticles can be as small as a few nanometer in diameter [10] and can therefore be encapsulated into the nanoscale structures of drug delivery vehicles. Nanoparticles of such small size even allows for inclusion in the lipid membranes of liposomes [21][22][23][24]. As mentioned, an efficient permeability barrier that can be modified for use in vesicular drug delivery vehicles is the cell mimetic membrane which has a hydrophobic membrane core surrounded by hydrophilic faces; drug delivery liposomes are smaller than 100 nm and comprise synthetic or natural lipids (Fig.…”

“…However, a very large excess of free sterylamine ligand that produced similar changes on its own puts a conclusive argument for nanoparticle effect on lipid ordering still out of reach. Bothun et al also provide an estimate of the capillary and vdW forces expected to arise between hydrophobically stabilized nanoparticles in a membrane based on a model for hydrophobic protein interactions in membranes [24]. It is found that steric stabilization through hydrophobic dispersants >1 nm will prevent aggregation through vdW interactions and that capillary forces will be longer range repulsive or attractive depending on if the lipid membrane is in the gel or liquid crystalline state.…”

Spatial SPION Localization in Liposome Membranes

“…However, precise characterization of these highly complex constructs is not straightforward. Von White G 2nd et al just recently demonstrated the impact of nanoparticles encapsulated in the liposomal membrane on its transition phase temperature (Tm) [22]. Standard characterization techniques,…”