Cell-type specific targeting of MNPs for directing cell fate and as a
cancer therapeutic.
PhD Supervisor(s): Dr James Dixon, Professor Alicia El Haj and Prof Kevin Shakesheff
This work will continue to translate the GET cell delivery technology (patent pending) to direct magnetic nanoparticle (MNP) targeting and uptake into stem cells. We have initiated a collaborative project to test this technology for targeting tumours in animal models with UCL ( who will conduct the first-in-man study for hyperthermal cancer therapy). This technology can also be applied to magnetic mechanical stimulation of cells.
During this project GET molecules (which are enhanced CPPs) will be utilised and modified to enable them to be used as a vector for the delivery of MNPs to cell membranes or intracellularly.
We are now at point where we can deliver MNPs pH- and enzyme-specifically. This project will finish the characterisation of this work and start development of cell-type specific targeting using binding of particular GAG types that are expressed differentially on cells. These will be produced and purified using bacterial, yeast or mammalian expression systems. These will be bound to particles and delivered to stem cells. Particle delivery will be monitored by microscopy techniques, as well as flow cytometric and biochemical approaches.
Nanoparticles targeted to cell membranes will be used exert forces on general membrane or cytoskeleton. This nanomagnetic ctuation will be achieved by applying static or time-variable magnetic fields. These forces will activate mechanosensitive processes directing cell behaviour. This work will be in collaboration with groups at Keele.
Nanoparticles targeted to intracellular locations will be used to load cells to target body sites (such as tumours) which can be activated to release cytotoxic compounds locally though heating by AC electromagnetic fields destroying the disease site (hyperthermic targeting). This project will involve interation and collaboration withthe UCL groups developing MNPs for cancer therapeutics. It will also involve the use of animal models and produciton of samples for in vivo testing, therefore this PhD will have a dynamic translational element.
