1. ¹Tumour Targeting Group, Academic Unit of Pathology, University of Sheffield Medical School, Sheffield, UK
2. ²Medway School of Pharmacy, University of Kent, Chatham Maritime, Kent, UK
3. ³Institute for Science and Technology in Medicine, Keele University School of Medicine, Stoke-on-Trent, UK
4. ⁴Department of Oral and Maxillofacial Surgery, University of Sheffield School of Clinical Dentistry, Claremont Crescent, Sheffield, UK
5. ⁵Academic Unit of Surgical Oncology, University of Sheffield Medical School, Sheffield, UK

Correspondence: Professor CE Lewis, Division of Genomic Medicine (Pathology), University of Sheffield Medical School, Beech Hill Road, Sheffield, Yorkshire S10 2RX, UK. E-mail: claire.lewis@sheffield.ac.uk

Received 12 September 2007; Revised 27 February 2008; Accepted 28 February 2008; Published online 17 April 2008.

Abstract

Attempts have been made to use various forms of cellular vectors to deliver therapeutic genes to diseased tissues like malignant tumours. However, this approach has proved problematic due to the poor uptake of these vectors by the target tissue. 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 for assessing monocyte extravasation, we show that the ability of transfected human monocytes to migrate across a human endothelial cell layer into a 3D tumour spheroid is markedly increased when cells are pre-loaded with MNPs and a magnetic force is applied close to the spheroid. 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.