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A novel magnetic approach to enhance the efficacy of cell-based gene therapies

Muthana, M., Scott, Simon D., Farrow, N., Morrow, F., Murdoch, C., Grubb, S., Brown, N., Dobson, J., Lewis, C.E. (2008) A novel magnetic approach to enhance the efficacy of cell-based gene therapies. Gene Therapy, 15 (12). pp. 902-910. ISSN 0969-7128. (doi:10.1038/gt.2008.57) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1038/gt.2008.57

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.

Item Type: Article
DOI/Identification number: 10.1038/gt.2008.57
Additional information: Unmapped bibliographic data: LA - English [Field not mapped to EPrints] J2 - Gene Ther. [Field not mapped to EPrints] C2 - 18418420 [Field not mapped to EPrints] AD - Tumour Targeting Group, Academic Unit of Pathology, University of Sheffield Medical School, Sheffield, United Kingdom [Field not mapped to EPrints] AD - Medway School of Pharmacy, University of Kent, Chatham Maritime, Kent, United Kingdom [Field not mapped to EPrints] AD - Institute for Science and Technology in Medicine, Keele University School of Medicine, Stoke-on-Trent, United Kingdom [Field not mapped to EPrints] AD - Department of Oral and Maxillofacial Surgery, University of Sheffield School of Clinical Dentistry, Claremont Crescent, Sheffield, United Kingdom [Field not mapped to EPrints] AD - Academic Unit of Surgical Oncology, University of Sheffield Medical School, Sheffield, United Kingdom [Field not mapped to EPrints] DB - Scopus [Field not mapped to EPrints]
Uncontrolled keywords: green fluorescent protein, magnetic nanoparticle, nanoparticle, animal experiment, article, cell based gene therapy, cell infiltration, cell migration, controlled study, endothelium cell, extravasation, gene targeting, human, human cell, male, monocyte, mouse, nanotechnology, nonhuman, nude mouse, priority journal, prostate cancer, solid tumor, Animals, Cell Adhesion, Cell Line, Tumor, Cell Movement, Cells, Cultured, Endothelial Cells, Flow Cytometry, Gene Therapy, Green Fluorescent Proteins, Humans, Iron, Magnetics, Male, Mice, Mice, Nude, Microscopy, Fluorescence, Monocytes, Nanoparticles, Neoplasms, Neoplasms, Experimental, Phagocytosis, Prostatic Neoplasms, Transfection, Xenograft Model Antitumor Assays, Mus
Subjects: R Medicine > R Medicine (General)
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Simon Scott
Date Deposited: 01 Dec 2017 14:43 UTC
Last Modified: 29 May 2019 13:52 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/45911 (The current URI for this page, for reference purposes)
Scott, Simon D.: https://orcid.org/0000-0002-8290-0461
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