’Hypersonic poration of membranes: from triggered release and encapsulation to drug delivery’
In this thesis hypersonic poration has been applied, to induce reversible membrane disruption in different assembled systems, such as: supported lipid bilayer (SLB), giant unilamellar vesicles (GUVs), polymer-shelled vesicles (PSVs) and cells.
‘Hypersonic poration can be used to control the permeability of cell membranes,’ Yao Lu says. ‘By inducing transient nanopores one may enhance the process of intracellular delivery, or control release/encapsulation processes better.’
The first two chapters of this thesis originated in Tianjin University. ‘Their expertise includes high frequency bulk acoustic wave devices,’ Yao says. ‘This new idea originated and was first published by our group in the journal of Small: Hypersonic Poration: A New Versatile Cell Poration Method to Enhance Cellular Uptake Using a Piezoelectric Nano-Electromechanical Device.’
Further, the behavior of a supported lipid bilayer (SLB) under the stimulation of hypersound, was analysed by real-time electrical measurements of hypersonic poration. Yao learnt that membrane permeability could be controlled by hypersound, creating instantaneous pore structures.
Also it was found that hypersound induces the reversible deformation of giant unilamellar vesicles (GUVs) within milliseconds. And the use of hypersound was shown to control the release and encapsulation of cargo from polymer-shelled vesicles (PSVs), either suspended in solution or immobilized on a surface.
The kinetics of release and encapsulation was analysed in order to reveal the dependence on hypersonic power. The mechanism of reversible membrane disruption was further verified with these hypersound-controlled processes, which created the possibility to realize pulsatile stimuli-responsive releases.
‘During the PhD project I’ve learnt to design useful experiments and make them significant for colleagues interested in the field,’ Yao says. ‘Approximately, I worked half of the time on perfecting the fluorescent measurement method, making sure all steps could be verified.’
This thesis has introduced a new physical poration method to noninvasively change the permeability of membranes. Hypersonic poration can be further developed, to achieve high spatial and temporal precision, Yao believes. ‘It promises to be a valuable way, to deliver various cargos to diverse cells on demand.’
Though this new physical method and technology is still far from direct application, Yao is excited regarding its potential use in the future. ‘It can be used in a lot of different kinds of tests,’ she says. ‘Chapter six has shown some promising results already. Hypersound is shown capable to enhance the delivery of drug-loaded carriers into cancer cells. It was revealed that mesoporous silica nanoparticles of approximately 160 nm, could be quickly internalized into cells, through direct penetration under the stimulation of hypersound, whereas larger particles were not taken up. I hope next PhD graduates will take up this really significant research direction.’
‘After my PhD Defense, I first will return to Tianjin University, to work on hypersonic poration in other applications, and finish my PhD in China,’ Yao says. ‘I prefer an academic career, as being a scientist always was a personal dream, discovering new phenomena and unravelling the mechanisms behind them. After graduation I will try to find a post-doc position within the field of biochemistry and biosensors.’
Yao spent a lot of time in the Mesa+ BioNano lab. ‘I was a frequent user of the Confocal Laser Scanning Microscope,’ she says. ‘I’m really grateful to the technicians, helping me to use the advanced equipment for my very specific research ends. Their expertise is indispensable, and they really showed great effort to understand the crucial details of my work, to come up with good suggestions.'