Use of nanomagnets to enhance monocyte delivery of gene therapy to tumours


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Munitta Muthana1, Simon Scott2, Craig Murdoch1, Neil Farrow3, Jon Dobson3, Claire Lewis1

1University of Sheffield, Sheffield, UK, 2University of Kent, Kent, UK, 3Keele University School of Medicine, Stoke on Trent, UK

Abstract

Use of nanomagnets to enhance monocyte delivery of gene therapy to tumours

Despite the development of sophisticated vectorology for gene therapy, effective delivery of such vectors to target tissues remains problematic. We have devised a novel way of using magnetic nanoparticles (MNPs) to enhance the uptake of such ‘therapeutically armed’ cells by tumours. Monocytes naturally migrate from the bloodstream into tumours so attempts have been made to use them to deliver therapeutic genes to these sites. However, transfected monocytes injected systemically fail to infiltrate tumours in large numbers.

Using a new in vitro assay we show; that MNPs are rapidly taken up by human monocytes without affecting their cell viability or migratory behaviour, monocytes transfected to express the reporter construct, GFP, and loaded with MNPs can cross the endothelial monolayer and infiltrate into spheroids (thereby mimicking their extravasation across the tumour vasculature into tumours), and application of an electromagnetic current close to spheroids enhanced the migration of these MNP-loaded cells across the endothelial barrier and improved spheroid infiltration. Furthermore, systemic administration of such ‘magnetic’ monocytes to mice bearing solid tumours led to a marked increase in their extravasation into the tumour in the presence of an external magnet.

This new magnetic targeting approach could be used to increase the targeting - and thus the efficacy - of many cell-based gene therapies in vivo.