<i>In vitro</i> gastrointestinal digestion increases the translocation of polystyrene nanoparticles in an <i>in vitro</i> intestinal co-culture model

<div><p></p><p>The conditions of the gastrointestinal tract may change the physicochemical properties of nanoparticles (NPs) and therewith the bioavailability of orally taken NPs. Therefore, we assessed the impact of <i>in vitro</i> gastrointestinal digestion on the protein corona of polystyrene NPs (PS-NPs) and their subsequent translocation across an <i>in vitro</i> intestinal barrier. A co-culture of intestinal Caco-2 and HT29-MTX cells was exposed to 50 nm PS-NPs of different charges (positive and negative) in two forms: pristine and digested in an <i>in vitro</i> gastrointestinal digestion model. <i>In vitro</i> digestion significantly increased the translocation of all, except the “neutral”, PS-NPs. Upon <i>in vitro</i> digestion, translocation was 4-fold higher for positively charged NPs and 80- and 1.7-fold higher for two types of negatively charged NPs. Digestion significantly reduced the amount of protein in the corona of three out of four types of NPs. This reduction of proteins was 4.8-fold for “neutral”, 3.5-fold for positively charged and 1.8-fold for one type of negatively charged PS-NPs. <i>In vitro</i> digestion also affected the composition of the protein corona of PS-NPs by decreasing the presence of higher molecular weight proteins and shifting the protein content of the corona to low molecular weight proteins. These findings are the first to report that <i>in vitro</i> gastrointestinal digestion significantly affects the protein corona and significantly increases the <i>in vitro</i> translocation of differently charged PS-NPs. These findings stress the importance of including the <i>in vitro</i> digestion in future <i>in vitro</i> intestinal translocation screening studies for risk assessment of orally taken NPs.</p></div>