Surface chemistry-mediated modulation of adsorbed albumin folding state specifies nanocarrier clearance by distinct macrophage subsets

Abstract

Controlling nanocarrier interactions with the immune system requires a thorough understanding of the surface properties that modulate protein adsorption in biological fluids, since the resulting protein corona redefines cellular interactions with nanocarrier surfaces. Albumin is initially the dominant protein to adsorb to nanobiomaterial surfaces, a process that is considered benign or beneficial by minimizing opsonization or inflammation. Here, we demonstrate the surface chemistry of a model self-assembled nanocarrier can be engineered to stabilize or denature the three-dimensional conformation of adsorbed albumin, which respectively promotes evasion or non-specific clearance in vivo. Interestingly, certain common chemistries that have long been considered to convey stealth properties were found to promote albumin recognition by macrophage class A1 scavenger receptors (SR-A1), providing a means for their eventual removal from systemic circulation. We establish that the surface chemistry of nanocarriers can be specified to modulate adsorbed albumin structure and thereby tune clearance by macrophage scavenger receptors.