Targeting Tumour Vasculature using Integrin αvβ3 - Observation of Liposome Accumulation in Microfluidic Vasculature Networks
Matthew Bourn a, Safoura Mohajerani b, Georgia Mavria b, Nicola Ingram b, P. Louise Coletta b, Stephen Evans a, Sally Peyman a b
a University of Leeds, School of Physics and Astronomy, Leeds, United Kingdom
b School of Medicine, University of Leeds
Proceedings of Emerging Investigators in Microfluidics Conference (EIMC)
Online, Spain, 2021 July 20th - 21st
Organizers: Adrian Nightingale, Darius Rackus and Claire Stanley
Oral, Matthew Bourn, presentation 024
Publication date: 5th July 2021

Integrin αvβ3, often referred to as the vitronectin receptor, is a cell-ECM adhesion protein highly expressed on activated endothelial cells found in newly formed blood vessels and, as a result, has been found to be crucial for angiogenesis. The constant pro-angiogenic signaling across the tumour microenvironment results in tumour vasculature expressing increased levels of αvβ3 compared to resting endothelial cells in normal tissue, therefore presenting αvβ3 as a potential site for the targeting of anti-cancer therapeutics 1.  Inhibition of αvβ3 signaling with RGD peptides or monoclonal antibodies has been observed to induce apoptosis in newly formed tumour vessels and reduce overall tumour growth however, little investigation into exploiting αvβ3 upregulation as a drug carrier target has been performed 2,3. This study uses self-assembled, perfusable vasculature networks grown within microfluidic devices to investigate the effectiveness of αvβ3 targeting 4. Tumour vasculature was recreated by conditioning networks with media taken from tumour cell cultures (TCM) which resulted in greater rates of angiogenesis compared to healthy networks. Flow cytometry revealed that growing endothelial cells in TCM resulted in increased rates of αvβ3 expression - as what would be expected in tumour vasculature. αvβ3-targeted liposomes were perfused through the networks and their accumulation within the vasculature quantified. Results observed increased accumulation in tumour conditioned networks compared to healthy networks – indicating that αvβ3 may be a suitable target for drug-loaded liposomes and allow for increased local drug delivery to the tumour site.

The authors would like to thank the EPSRC for funding this project. 

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