Nanoparticle Delivery in a Human Pancreatic Ductal Adenocarcinoma-on-a-Chip Model

There is a growing demand for therapies, personalized treatments, and diagnostic approaches for pancreatic ductal adenocarcinoma (PDAC). To address this, human pancreatic organoids have been developed to model the pancreas and enrich patient PDAC cells, which can be incorporated into organ-on-a-chip (OOC) systems. With or without an endothelial barrier, these systems offer constant physiological flow essential for ductal epithelial structures and can be used for nanoparticle transport and delivery studies. This study aimed to establish a PDAC OOC with a functional endothelial layer to assess barrier function and nanoparticle transport. Using primary human PDAC organoids and Human Umbilical Vein Endothelial Cells (HUVEC) in a vertically stacked chip design, we cultured cells under varying media flows and evaluated nanoparticle permeability. We successfully maintained PDAC OOC systems with endothelial cells for several weeks, facilitating repeated compound and nanoparticle transport studies, highlighting the potential of nanoparticles in theranostics and the utility of OOCs as study platforms.