Tumour-on-a-chip provides an optical window into nanoparticle tissue transport

Nanomaterials are used for numerous biomedical applications, but the selection of optimal properties for maximum delivery remains challenging. Thus, there is a significant interest in elucidating the nano-bio interactions underlying tissue accumulation. To date, researchers have relied on cell culture or animal models to study nano-bio interactions. However, cell cultures lack the complexity of biological tissues and animal models are prohibitively slow and expensive. Here we report a tumour-on-a-chip system where incorporation of tumour-like spheroids into a microfluidic channel permits real-time analysis of nanoparticle accumulation at physiological flow conditions. We show that penetration of nanoparticles into the tissue is limited by their diameter and retention can be improved by receptor-targeting. Nanoparticle transport is predominantly diffusion-limited with convection increasing accumulation exclusively at the tissue perimeter. A murine tumour model confirms these findings and demonstrates that the tumour-on-a-chip can be useful for screening optimal nanoparticle designs prior to in vivo studies.