projects - Keele University

Current Projects

Keele Research Group in Magnetism and Magnetic Materials Techniques

NANOMAGNETIC ACTUATION

In this work, magnetic nanoparticles are being used to target and manipulate cellular processes and functions and to control stem cell differentiation, primarily through the activation of ion channels. Magnetic nanoparticles are coated with a functionalizable polymer (such as silica, PVA, or dextran) to which antigens are bound. These antigens may target either specific ion channels, such as the TREK-1 potassium channel, or more non-specific receptors such as surface integrins. By applying a static or time-varying magnetic field, forces exerted on the particles activate either specific ion channels or general membrane and cytoskeleta deformation activates adjacent mechanosensitive ion channels, initiating biochemical processes within the cell.

GENE TRANSFECTION

With the sequencing of the human genome and the advent of gene therapy has come the need to develop effective delivery and transfection agents. These agents must be able to target therapeutic and reporter genes to the relevant cells and organs both in vitro for basic investigations as well as in vivo for therapeutic applications. Recent safety concerns over the use of viral vectors has begun to shift the emphasis toward the development of non-viral delivery agents, primarily cationic lipids. Professor Dobson’s group has been working on the development of a novel magnetic nanoparticle-based gene transfection system based on oscillating arrays of magnets. We have now built a prototype of the system. In these magnefect systems, DNA is attached to magnetic nanoparticles and oscillating arrays of magnets placed underneath a Petri dish (in the case of in vitro transfection) are used to stimulate particle uptake and gene expression and to drastically reduce transfection time. Prototype systems have been shown to improve in vitro transfection efficiency (up to 10x) in human airway epithelial cells compared to static magnet systems and, depending on the transfection time, up to 100x compared to “gold standard” cationic lipids during test runs. We are also working on the developoment of novel magnet arrays to improve efficiency.

MAGNETIC CELL TARGETING AND HYPERTHERMIA

The aim of this work is to load cells with biocompatible magnetic nanoparticle and re-introduce them into the body, using magnets to target them to repair sites or tumours. Human mesenchymal stem cells have been successfully targeted to wound sites in a mouse model. A variation on the technique uses magnetic nanoparticle-loaded human macrophages to target these cells to the non-vascularized, hypoxic cores of solid tumours. Once there, the cells deliver a payload of cytotoxic compounds or “suicide” genes. Once the drug or therapeutic gene has been delivered, AC electromagnetic fields are used to heat the particles, destroying the macrophages before they build a new blood supply to the tumour core.

MAGNETIC NANOPARTICLE SYNTHESIS AND CHARACTERIZATION

Professor Dobson’s group is also active in the development of techniques for the synthesis of novel magnetic nanoparticles for biomedical applications. This work focuses on producing particles with enhanced magnetic properties or surface chemistry, as well as investigating new methods for enhanced DNA loading. Techniques such as High-Resolution Transmission Electron Microscopy and Superconducting Quantum Interference Device magnetometry are used for characterization of the particles.

IRON COMPOUNDS AND NEURODEGENERATIVE DISEASE

We have a large, international research programme aimed at developing imaging and characterization techniques for iron compounds in neurodegenerative diseases such as Alzheimer’s and Parkinson’s, to inform the development of MRI-based early diagnostic techniques and to guide the development of chelation therapies. This work involves MRI signal validation using synchrotron x-ray analysis as well as investigations of iron compounds and their magnetic properties using Superconducting Quantum Interference Device (SQUID) magnetometry. This work is conducted in collaboration with the US National High Magnetic Field Laboraotry at the University of Florida, the Advanced Photon Source Synchrotron at Argonne National Laboratory and the DIAMOND synchrotron in Oxfordshire.