Differential Roles of the Protein Corona in the Cellular Uptake of Nanoporous Polymer Particles by Monocyte and Macrophage Cell Lines

Abstract

Many biomolecules, mainly proteins, adsorb onto polymer particles to form a dynamic protein corona in biological environments. The protein corona can significantly influence particle-cell interactions, including internalization and pathway activation. In this work, we demonstrate the differential roles of a given protein corona formed in cell culture media in particle uptake by monocytes and macrophages. By exposing disulfide-stabilized poly(methacrylic acid) nanoporous polymer particles (PMASH NPPs) to complete cell growth media containing 10% fetal bovine serum, a protein corona, with the most abundant component being bovine serum albumin, was characterized. Upon adsorption onto the PMASH NPPs, native bovine serum albumin (BSA) was found to undergo conformational changes. The denatured BSA led to a significant decrease in internalization efficiency in human monocytic cells, THP-1, compared with the bare particles, due to reduced cell membrane adhesion. In contrast, the unfolded BSA on the NPPs triggered class A scavenger receptor-mediated phagocytosis in differentiated macrophage-like cells (dTHP-1) without a significant impact on the overall internalization efficiency. Taken together, this work demonstrates the disparate effects of a given protein corona on particle-cell interactions, highlighting the correlation between protein corona conformation in situ and relevant biological characteristics for biological functionalities.

The Impact of Nanoparticle Protein Corona on Cytotoxicity, Immunotoxicity and Target Drug Delivery

“…Macrophages, considered the main players in the clearance of NPs from tissues, use phagocytosis to internalize NP-PC complexes, while naked NPs can be taken up through other mechanisms (i.e., clathrin-and dynamin-dependent endocytosis) [130]. In evaluating the inflammatory effects of NPs and their PC in monocyte cell lines in vitro, it is important to induce monocyte differentiation to a macrophage phenotype.…”

“…In evaluating the inflammatory effects of NPs and their PC in monocyte cell lines in vitro, it is important to induce monocyte differentiation to a macrophage phenotype. Macrophages displayed a completely different profile of secreted inflammatory cytokines compared with undifferentiated monocytes when treated with PC-coated NPs [130]. Such leukocytes as macrophages, dendritic cells, eosinophils, neutrophils and mast cells express on their surface the Fc receptor, which binds with high-affinity opsonized material through the crystallizable fragment region of the antibodies.…”

“…The different role of protein corona in nanoparticle uptake by monocytes and macrophages is represented. Reproduced with permission from [134]. ing clear that the PC also mediates and has the ability to alter the immune response.…”

Particle Targeting in Complex Biological Media

“…[19c,99,101] For instance, Yan et al has reported that unfolded albumin adsorbed on particles triggers class A scavenger receptor-mediated phagocytosis in differentiated macrophage-like (dTHP-1) cells. [99] Mortimer et al also reported the role of unfolded albumin in cellular uptake of the protein-NP complex by dTHP-1 cells, and highlighted that denatured albumin and other serum proteins can promote the clearance of particles from circulation via the MPS. [101] In addition, opsonins, which are present in plasma, can promote the recognition of particles by the immune system and the phagocytosis of particles by macrophages.…”

“…[15,94,99] Therefore, to retain the targeting ability of particles in a biological environment, the goal is to better understand the formation and effects of protein coronas in order to eliminate their negative impacts on in vivo particle targeting and behavior. [21b,89c,123] Low-fouling materials (e.g., PEG, zwitterionic polymers and carbohydrates) have been extensively used to confer the carrier surface with stealth properties and can significantly reduce the amount of adsorbed proteins on the particle surface.…”