How particles enter the body: investigating particle-barrier interactions in the digestive tract (PARENTRY)

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In the first funding period, we (i) successfully developed tailor-made quantum dots (QDs) with highly defined emission spectra and specific chemical surface properties, (ii) built-up novel multi-dimensional imaging modes for in-tissue tracking of nanoparticles (NPs) by intravital 2-photon microscopy, (iii) characterized the interaction of NPs with mucus and intestinal fluids, and (iiii) identified pathways along which NPs enter the gut mucosa. In the second funding period, we will apply this knowledge and instrumentation to the whole digestive tract. Because most NPs proved to alter size and surface characteristics upon contact with gastrointestinal matter, the “ingestion history” of an NP might critically affect its mucosal uptake. We therefore will extend our unique imaging approach to other sections of the digestive tract (oral cavity, esophagus, stomach, large intestine), include the effect of bacterial colonization and invasion, and study the implications of mucosal inflammation. With the new generation of strongly emitting quantum dot/quantum rods (QD/QRs) developed in the first funding period, the NP detection sensitivity in complex tissues will be increased. Single particle imaging will also be achieved by extending the non-linear imaging to the near IR which avoids background fluorescence. We will cover the NP size range from 20–100 nm with uniform surface chemistry. By combining our imaging approach with a novel intestinal explant model and total body quantitation of NP uptake, we attempt to determine the absolute amount and percentage of NPs taken up in the different sections of the digestive tract. Controlled variation of NP properties, will allow us to predict the most probable site of entry and extent of uptake as a function of NP size, shape and surface properties.