Magnetic nanoparticles will produce heat if exposed to an alternating magnetic field. If magnetic nanoparticles can get inside a tumour, an alternating magnetic field can be applied so that the particles heat up and the tumour cells are killed. This project investigated two different ways to deliver nanoparticles into the tumour using mesenchymal stem cells. One worked, one didn’t, and the group has now secured future funding to keep investigating the method that proved successful.
Development of Magnetic Nanoparticle Bearing Mesenchymal Stem Cells For Magnetic Hyperthermia Treatment of Sarcomas
Recently, there has been interest in the use of magnetic hyperthermia for the treatment of a number of solid tumours including brain cancers, where initial studies have shown potential. Magnetic hyperthermia is based on the observation that when magnetic (iron) nanoparticles (MNPs) are exposed to an alternating magnetic field (AMF) energy is rapidly released as heat. In clinical hyperthermia therapy, the theory is that, when MNPs are delivered to a tumour and an AMF of well-chosen amplitude and frequency is applied, heat is generated locally killing the tumour cells. The short exposure of AMF required to induce heat in a tumour loaded with MNPs is non-toxic to adjacent MNP-free tissues and can allow repeated application safely.
In this pilot study we looked at the potential of using mesenchymal stem cells (MSCs) to act as a delivery system for carriage of MNPs to sarcomas to facilitate magnetic hyperthermia treatment. MSCs were loaded with manufactured MNPs or stimulated to make their own MNPs directly by a novel genetic engineering strategy. These cells were exposed to an AMF either alone or in culture with an osteosarcoma cell line and the extent of cell death of the MSCs and co-cultured sarcoma cells assessed.
We were unable to show any effect on cell viability/death when MSCs loaded with commercially available MNPs were subjected to an AMF. However, when MSCs which had been genetically modified to produce MNPs were exposed to an AMF we found that around 50% of the cells died. When MNP-producing MSCs were mixed with osteosarcoma cells and exposed to an AMF around 50% of the MSCs and sarcoma cells were killed. AMF alone had no effect on MSC and sarcoma cell viability in the absence of MNPs.
Magnetic hyperthermia therapy is currently in its infancy with improvements being required in delivery of the magnetic nanoparticles to the site of tumour growth and significant technological developments in the application of an AMF to patients in the clinic. These results indicate however that magnetic hyperthermia has potential as an adjunct to current treatments in the management of sarcoma once the practical difficulties of bringing the technology to the clinic are met.
- Further funding of ~ £25,000 secured from the Jamie King Urological Cancer Research Fund. For project entitled: Magnetic Nanoparticle Bearing Mesenchymal Stromal Cells for Radiosensitisation. 2017.
- Sarcoma UK Article: Research breakthrough at the University of Edinburgh. Published online on the Sarcoma UK website on 21 August 2017.