A Novel Magnetic Approach to Enhance the Efficacy of Cell-Based Gene Therapies

Gene Ther. 2008 Jun;15(12):902-10. doi: 10.1038/gt.2008.57. Epub 2008 Apr 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Cells, Cultured
  • Endothelial Cells / physiology
  • Flow Cytometry
  • Genetic Therapy / methods*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Iron
  • Magnetics*
  • Male
  • Mice
  • Mice, Nude
  • Microscopy, Fluorescence
  • Monocytes / metabolism*
  • Nanoparticles*
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / therapy
  • Phagocytosis
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy
  • Transfection
  • Xenograft Model Antitumor Assays

Substances

  • Green Fluorescent Proteins
  • Iron