Low uptake of silica nanoparticles in Caco-2 intestinal epithelial barriers

Cellular barriers, such as the skin, the lung epithelium or the intestinal epithelium, constitute one of the first obstacles facingnanomedicines or other nanoparticles entering organisms. It is thus important to assess the capacity of nanoparticles to enter andtransport across such barriers. In this work, Caco-2 intestinal epithelial cells were used as a well-established model for the intestinalbarrier, and the uptake, trafficking and translocation of model silica nanoparticles of different sizes were investigated using a com-bination of imaging, flow cytometry and transport studies. Compared to typical observations in standard cell lines commonly usedfor in vitro studies, silica nanoparticle uptake into well-developed Caco-2 cellular barriers was found to be very low. Instead, nano-particle association to the apical outer membrane was substantial and these particles could easily be misinterpreted as internalised inthe absence of imaging. Passage of nanoparticles through the barrier was very limited, suggesting that the low amount of inter-nalised nanoparticles was due to reduced uptake into cells, rather than a considerable transport through them