Differential uptake of functionalized polystyrene nanoparticles by human macrophages and monocytic cells

Abstract

Tumor cell lines are frequently used as models to analyze the cellular uptake of nanoparticles. Here we show that carboxy‐ (PS‐COOH) and amino‐functionalized (PS‐NH2) polystyrene nanoparticles of ~100 nm in diameter are internalized by human macrophages, THP‐1 monocytic leukemia cells, and by PMA‐differentiated THP‐1 cells via different mechanisms. Macrophages and THP‐1 rapidly internalized PS‐COOH and to a lesser extent PS‐NH2 particles when incubated in buffer. The uptake of both nanoparticles was drastically reduced in media containing serum. Using pharmacological and antisense in vitro knockdown approaches, we showed that the specific interaction between the CD64 receptor and the particles determines the macrophage uptake of particles by phagocytosis, whereas particle internalization in THP‐1 cells occurred via dynamin II‐dependent endocytosis. PMA‐differentiated THP‐1 cells took up the particles via macropinocytosis. In line with the in vitro data, more PS‐COOH particles were accumulated in liver tissue, whereas PS‐NH2 particles were preferentially targeted to tumor tissue. These data show that the extent of the particle internalization, the uptake kinetics and its mechanism differ significantly among primary cells and model tumor cells, whether differentiated or not, and are further critically dependent on the particle opsonisation by serum proteins. Supported by the DFG, SPP1313.