title: Tumour-on-a-chip provides an optical window into nanoparticle tissue transport.
abstract: 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 (NP) accumulation at physiological flow conditions. We show that penetration of NPs into the tissue is limited by their diameter and that retention can be improved by receptor targeting. NP transport is predominantly diffusion-limited with convection improving accumulation mostly 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 NP designs prior to in vivo studies.
authors.affiliation: 1] Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada [2] Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada [3].
authors.forename: Alexandre
authors.initials: A
authors.lastname: Albanese
authors.forename: Alan K
authors.initials: AK
authors.lastname: Lam
authors.forename: Edward A
authors.initials: EA
authors.lastname: Sykes
authors.forename: Jonathan V
authors.initials: JV
authors.lastname: Rocheleau
authors.forename: Warren C W
authors.initials: WC
authors.lastname: Chan
mesh_terms: D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D003094:Collagen / Q000737:chemistry; D004058:Diffusion; D004338:Drug Combinations; D004867:Equipment Design; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007797:Laminin / Q000737:chemistry; D051379:Mice; D046210:Microfluidic Analytical Techniques; D044085:Microfluidics / Q000379:methods; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D009368:Neoplasm Transplantation; D055095:Optics and Photonics; D011509:Proteoglycans / Q000737:chemistry; D016622:Silver Staining; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D004338:Drug Combinations; D005456:Fluorescent Dyes; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen