Non-specific biomolecular surfaces and macrophage uptake mechanisms

Non-specific biomolecular surfaces and macrophage uptake mechanisms refer to the complex series of physical and biological events that occur when foreign entities, such as nanoparticles or medical implants, encounter biological fluids and immune cells [1]. Upon entry into the bloodstream, these surfaces are rapidly coated by a layer of host proteins known as the protein corona, which includes opsonins like immunoglobulins and complement factors [2]. This opsonization facilitates recognition and internalization by macrophages of the mononuclear phagocyte system (MPS) through various endocytic and phagocytic pathways [3]. In the context of drug delivery, these mechanisms are often viewed as barriers that lead to rapid systemic clearance and off-target accumulation in the liver and spleen [4]. Conversely, in immunotherapy, these pathways are intentionally engaged to deliver agents directly to macrophages to modulate the immune microenvironment [5]. Understanding these non-specific interactions is critical for the design of "stealth" coatings, such as PEGylation, which aim to minimize protein adsorption and extend the circulation time of therapeutic agents [1, 3]. Citations: [1] Walkey, C. D., & Chan, W. C. (2012). Chem. Soc. Rev. [2] Moore, T. L., et al. (2015). Chem. Soc. Rev. [3] Gustafson, H. H., et al. (2015). Nano Today. [4] Moghimi, S. M., et al. (2001). Pharmacol. Rev. [5] Szakács, G., et al. (2006). Nat. Rev. Drug Discov.

Other names

OpsonizationProtein corona formationPhagocytic clearanceMononuclear Phagocyte System (MPS) uptakeReticuloendothelial System (RES) clearance

Reduction of non-specific protein adsorption (stealthing) to prevent recognition by opsonins and subsequent macrophage internalization.