(198v) The Implications of Competitive Adsorption on Lipoprotein-Nanoparticle Biodistribution

Nanoparticles introduced into the bloodstream are exposed to thousands of proteins that are competing for their surfaces. During transport, this competition changes the amount and class of proteins that are bound to the nanoparticle surface. High density lipoproteins (HDLs) have been shown to bind nanoparticle surfaces of different sizes and chemistries, but quantitative values are lacking. Bound HDLs could change the biodistribution of nanoparticles if the interaction is stable and HDLs retain their functionality. We determined equilibrium binding parameters for HDLs and nanoparticles using gel electrophoresis and a quantitative model of protein-sphere interactions. We used polystyrene spheres - pristine, carboxylate-modified, and amine-modified - as model nanoparticles. ApoAI – the main structural protein of HDLs - had the following affinities for the nanoparticles: K_d-COOH ~1.1 µM, K_d-NH2 ~1.9 µM, K_d-PS ~3.1 µM). Interestingly, although there is relatively strong binding of ApoAI to PSNH₂, ApoAI does not completely saturate the nanoparticle surface at constant plasma concentration and increasing nanoparticle concentrations. These results provide insight into the complexities involved in the binding kinetics of lipoproteins to nanoparticles and the need to flesh out the possible involvement of lipoproteins in redirecting nanoparticle drug delivery vehicles to HDL receptors on the liver.