Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy

Abstract

Proteins bind the surfaces of nanoparticles, and biological materials in general, immediately upon introduction of the materials into a physiological environment. The further biological response of the body is influenced by the nanoparticle-protein complex. The nanoparticle's composition and surface chemistry dictate the extent and specificity of protein binding. Protein binding is one of the key elements that affects biodistribution of the nanoparticles throughout the body. Here we review recent research on nanoparticle physicochemical properties important for protein binding, techniques for isolation and identification of nanoparticle-bound proteins, and how these proteins can influence particle biodistribution and biocompatibility. Understanding the nanoparticle-protein complex is necessary for control and manipulation of protein binding, and allows for improved engineering of nanoparticles with favorable bioavailability and biodistribution.

Fig. 1

Example of a 2D protein gel used for protein identification. The protein adsorption pattern was analyzed for a sample of 30 nm colloidal gold. The colloidal gold sample was incubated with human plasma and then recovered by centrifugation. The proteins bound to the nanoparticles were separated by 2D gel electrophoresis.

Fig. 2

Biodistribution of nanoparticles with varying coatings and bound proteins. Uncoated particles bind proteins and are taken up by the RES into the liver and spleen. “PEGylated” particles bind very few proteins, avoid uptake by the RES, and are longer circulating in the blood. “Polysorbate-coated” particles can specifically bind ApoE and selectively target to the brain across the blood brain barrier.