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

TLDR

Protein coronas form on polymer particles in biological media and can alter particle–cell interactions, including uptake pathways. This study investigates how a single protein corona influences uptake of nanoporous polymer particles by monocytes versus macrophages. Disulfide‑stabilized poly(methacrylic acid) nanoporous polymer particles were incubated in 10 % fetal bovine serum media, forming a corona dominated by bovine serum albumin that was characterized. Conformational changes in adsorbed BSA reduced internalization in THP‑1 monocytes by decreasing membrane adhesion, while the unfolded BSA promoted scavenger‑receptor–mediated phagocytosis in differentiated macrophage‑like dTHP‑1 cells without altering overall uptake, demonstrating that corona conformation dictates cell‑specific uptake.

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.