Haofei Wang
The University of Queensland, Australia
Title: Tumor-Vasculature-on-a-Chip for studying transport of nanoparticles
Biography
Biography: Haofei Wang
Abstract
Nanoparticles’ extravasation and tumor accumulation play critical roles in nanoparticle-based drug delivery, but the underlying mechanism, such as the effects of particle size, stiffness and targeting ligands, remains largely unexplored due to the lack of reliable tumor models. Here we report a microfluidic Tumor-Vasculature-on-a-Chip (TVOC) mimicking the tumor microenvironment, mainly the tumor leaky vasculature and tumor tissue, to study the transport of nanoparticles. By culturing endothelial cells and tumor cells in independent channels, TVOC recreates the endothelial barrier and dense tumor ECM, which are the two main biological barriers involved in the extravasation and tissue penetration of nanoparticles. With the use of real-time imaging, the transports of nanoparticles across individual modeled barriers were systematically investigated and different transport kinetics was observed. The results suggested the similar barrier properties of engineered tumor vasculature and dense ECM in hindering the delivery of nanoparticles. The tumor accumulation of nanoparticles was evaluated using tumor spheroids and the results were comparable to results obtained in animal models, which quantitatively validated the TVOC in predicting the performance of nanoparticles in vivo. We show that the TVOC could be used as a powerful platform to evaluate the transport of various nanoparticles at specifically-tuned biological conditions in vitro, which could provide valuable information on future design of nanoparticle-based drug delivery systems with no use of detailed animal experiments.