Effects of true to life polyethylene terephthalate and polycaprolactone nanoparticles on macrophages under a repeated exposure mode

Micro and nanoplastics are pollutants which concentration in different biotopes increases continuously over time, which poses the question of their potential effects on health. In animals, these micro and nanoplastics are recognized as particulate materials and thus handled by macrophages,which are therefore a key cell type to study. Most studies have used an experimental scheme in which the cells of interest are exposed to a single dose of plastics, and where the readout of the studied parameters is made immediately after exposure. However, this classical experimental scheme does not take into account the impact of biopersistence, nor the potential cellular adaptation that may take place when cells are exposed repeatedly to a low dose of plastics. We thus used a repeated exposure scheme, in order to better take into account these phenomena. Within this frame, we compared the macrophages responses to a persistent nanoplastic, i.e. true-to-life polyethylene terephthalate nanoparticles and to a biodegradable nanoplastic, i.e. polycaprolactone, by a combination of proteomic and targeted experiments. Our results show that under this repeated exposure scheme, the proteome changes were of a lesser extent than under the acute exposure mode, indicating cell adaptation. However, polyethylene terephthalate nanoparticles induced oxidative stress, a slight depression of phagocytosis and a pro-inflammatory response, while polycaprolactone nanoparticles induced a depression of macrophages functions, especially regarding cytokines production (Interleukin 6, MCP-1, TNF alpha) in response to a bacterial challenge (represented by a lipopolysaccharide challenge), indicating harmful but different effects of both nanoplastics even in the repeated exposure scheme. • PET and PCL nanoparticles are intensively internalized by macrophages under a repeated exposure mode. • Under a repeated exposure mode, PET nanoparticles induce a pro-inflammatory response in macrophages. • Under a repeated exposure mode, PCL nanoparticles induce a depression of responses in macrophages. • The responses induced by PET and PCL nanoparticles under a repeated exposure mode are different from those induced in an acute exposure mode.