Differential Recognition of Nanoparticle Protein Corona and Modified Low-Density Lipoprotein by Macrophage Receptor with Collagenous Structure

Key practical challenges such as understanding the immunological processes at the nanoscale and controlling the targeting and accumulation of nano-objects in vivo now further stimulate efforts to underpin phenomenological knowledge of the nanoscale with more mechanistic and molecular insight. Thus, the question as to what constitutes nanoscale biological identity continues to evolve. Certainly nanoparticles in contact with a complex biological milieu develop a biological identity, differing from the original nanomaterial, now referred to as the “biomolecular corona”. However, this surface-adsorbed layer of biomolecules may in some circumstance lead to different forms of receptor–particle interactions not evident only from the identity of the surface-adsorbed biomolecules and hard to predict or detect by current physicochemical methods. Here we show that scavenger receptors may recognize complex as yet unidentified biomolecular surface layer motifs, even when no current physicochemical analysis is capable of doing so. For instance, fluorescently labeled SiO2 nanoparticles in a biological milieu are strongly recognized by the macrophage receptor with collagenous structure (MARCO) in even dense biological media (human serum) apparently using a form of binding with which most of the MARCO’s known ligands (e.g., LPS, modified LDL) fail to compete. Such observations may suggest the need for a much stronger emphasis on nanoscale receptor–corona and other biomolecular interaction studies if one wishes to unravel how biomolecular recognition drives outcomes in the nanoscale biological domain.