Ultrasound and Microbubbles can Lodge qDots into Murine ex-vivo Small Intestine

Ultrasound (US) and microbubbles (MBs) can deliver drugs to epithelial tissue layers. Previous in vivo work was inconclusive as to whether US + MBs can promote delivery of fluorescent quantum dots (qDots) to intestinal tissue covered by a layer of mucus. The objectives of the present work was (1) to identify a suitable fixative for preserving the mucus layer on the epithelial tissue to enable imaging after US + MB treatment and (2) to verify the depth of penetration of qDots in the small intestine when qDots are delivered in the presence of US + MBs. The mucosa of three murine small intestines were insonated with a 4.18 MHz miniature focused US transducer for 90 s (1 MPa PNP, MI = 0.5) while simultaneously delivering a suspension of qDots and MBs. Fixing tissue with PFA rather than Carnoy was more appropriate for detecting retention of qDots in the mucus layer. Two-photon laser scanning microscopy showed that qDots lodged in mucus, but did not penetrate the underlying intestinal tissue. This indicates that the parameters used for US + MBs were suitable only for delivering qDots into the mucus layer. The finding suggests focused US + MBs + qDots could be used to mark specific intestinal locations which could enable clinicians to target subsequent therapeutic or surgical interventions to the same diseased sites within a short time afterwards.