Biological barriers and current strategies for modifying nanoparticle bioavailability.

Nanoparticles are diligently crafted with exacting control over size, shape, and composition. The pristine nanoparticles are rigorously characterized in vitro by numerous physical and materials science techniques. Immediately after being exposed to body fluids, nanoparticles interact with a heterogeneous mixture of proteins and numerous different cell types that modify the nanoparticle surface and affect their bioavailability. Understanding the mechanisms behind the recognition and elimination of these modified nanoparticles is the key to the successful translation of nanomaterials from preclinical to clinical applications. This paper reviews the anatomy of the primary organs (kidney, liver, and spleen) responsible for nanoparticle bioelimination and the components of the innate immune system (complement system and scavenger receptors) that indirectly and directly recognize nanoparticles as foreign. Recent results using PEG as a steric barrier, generating biomimetic nanoparticles, and the effect of nanoparticle material properties to increase the bioavailability of nanoparticles are presented.