Lipid bilayer-nanoparticle interactions in nanotoxicology and nanomedicine.

摘要

Nanoparticle (NP) interactions that may destabilize cell membranes and cause toxicity can also be used to design and control therapeutic assemblies. Fundamentally examining interactions between NPs and cell membranes is crucial to understanding NP toxicity mechanisms and the development of safe and non-toxic NP-based commercial and therapeutic applications. In this dissertation it is demonstrated that self-assembled lipid bilayers can be employed as model membranes to determine NP interact ions.;Hydrophobic NPs can embed within lipid bilayers and lead to size-dependent lipid disordering. Chapter 3 demonstrates that C60 fullerene can be embedded within dipalmitoylphosphatidylcholine (DPPC) lipid bilayers and induce changes in liposome structure, lipid melting, and fluidity. C 60 not embedded within the bilayers formed nanoscale C60 aggregates (nano-C60) outside of the liposomes. In addition to membrane destabilization, the lipid-assisted REV method allowed for higher aqueous C60 concentrations and the rapid formation of nano-C 60 with less solvent consumption compared to solvent exchange methods. Chapter 4 demonstrates the formation, characterization, and release properties of bilayer-decorated magnetoliposomes (dMLs) that were prepared by embedding small hydrophobic SPIO NPs at different lipid molecule to NP ratios within DPPC bilayers. It is shown that dMLs not only exhibit lower spontaneous leakage of encapsulated molecules relative to control liposomes, but the leakage can be increased and tuned by employing radio frequency heating.;Hydrophilic NP binding at lipid/water interfaces can lead to lipid reordering, lipid extraction, and bilayer pore formation. In chapter 5, interactions between negative charged NPs (hydrophilic SPIO at diameters of 16, 30, and 58 nm) and cationic liposomes revealed that these interactions were NP size-dependant.;First, protocols were developed for examining hydrophobic and hydrophilic NP-bilayer interactions using lipid bilayer vesicles or liposomes. Second, interactions between liposomes and NPs were characterized by examining changes in liposome structure, morphology, phase behavior, and permeability. Third, the ability to exploit these interactions for the design of novel NP-decorated liposomes has been demonstrated.