Friday, 17 September, 13:00

Speaker:  

Dr John Mulvihill, University of Limerick

Speaker Profile 

Dr Mulvihill is a Lecturer in Biomedical Engineering at the University of Limerick. He was a Marie Curie fellow at Georgia Institute of Technology, USA, and Trinity College Dublin in the area of cell mechanobiology, and has worked as part of the FP7-funded (€8.7million) AMCARE project. His research focuses primarily on cellular mechanobiology and the role mechanics plays in cellular function. In particular, he aims to investigate the transport of nanoparticles across the blood-brain barrier into the central nervous system as vehicles for drug delivery and diagnostics. Since 2012, he has over 40 peer-reviewed publications and 4 book chapters. He has a h-index of 16 and an i10 of 21.

Abstract 

Treatment of glioblastoma, a brain cancer with a high mortality rate, is severely complicated by difficulties associated with delivering therapeutics to the brain and rapid, diffuse invasion of the tumour cells throughout the brain. Nanomedicine is believed to have the potential to overcome challenges with therapeutic delivery. However, the field lacks standardisation which complicates elucidating nanoparticle properties that facilitate safe, effective delivery to the brain. Our work attempted to determine standard techniques for a repeatable method of comparing nanoparticles and their ability to cross the blood-brain barrier (BBB).

To address this, we synthesized a range of materials across different sizes. These particles were characterised using standard techniques in water, to determine the properties of the newly synthesised nanoparticles, and in media and serum, to clarify how nanoparticle properties change in physiological environments. The nanoparticles were then tested on BBB model which was prepared using a method of serum starvation, found to result in barrier resistances that closely resemble the native BBB (3000-4000 Ω.cm2 in vitro, 2000-5000 Ω.cm2 in vitro).

It was found that the properties of nanoparticles, in particular nanoparticle zeta potential, determined in media, not water, correlated well with the interaction of nanoparticles and the BBB including nanoparticle permeability and effects on neurovascular cells viability. In particular, Fe2O3 nanoparticles, which have media-based zeta potentials between -10 and -12 mV, are capable of good BBB penetration with minimal changes to cell viability. This nanoparticle could be useful for the delivery of therapeutics to glioblastoma. However, the reasons for tumour cell invasion must still be addressed.

The role for biomechanics, in particular compressive loading, brought about in vivo by increased cranial stresses resulting from tumour growth, were investigated. The migration speed of glioblastoma cells significantly increases in response to compressive loading. This represents a potential unexploited avenue for treatment that has not previously been explored. The use of nanoparticles to inhibit glioblastoma invasion, stimulated by compressive loading, could help to improve the survival rates associated with this deadly cancer.