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

• Published in: Nature communications Vol. 12; no. 1; pp. 648 - 18
• Main Authors: Vincent, Michael P, Bobbala, Sharan, Karabin, Nicholas B, Frey, Molly, Liu, Yugang, Navidzadeh, Justin O, Stack, Trevor, Scott, Evan A
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 28.01.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Adsorption; Albumin; Albumins; Animals; BASIC BIOLOGICAL SCIENCES; Cattle; Computational fluid dynamics; Cryoelectron Microscopy; Drug carriers; Drug delivery; Humans; Immune clearance; Immune system; Inflammation; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Kinetics; Macrophages; Macrophages - metabolism; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Opsonization; Protein adsorption; Protein Corona - chemistry; Protein Corona - metabolism; Protein Folding; Proteins; RAW 264.7 Cells; Receptors; Receptors, Scavenger - chemistry; Receptors, Scavenger - metabolism; Scavenger receptors; Serum Albumin, Bovine - chemistry; Serum Albumin, Bovine - metabolism; Surface chemistry; Surface Properties; Three dimensional models
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-20886-7

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 one of the dominant proteins to adsorb to nanocarrier surfaces, a process that is considered benign or beneficial by minimizing opsonization or inflammation. Here, we demonstrate the surface chemistry of a model 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 denature albumin to promote nanocarrier recognition by macrophage class A1 scavenger receptors, 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.