Self-assembling Liposome Nano-transducers

Lead Research Organisation: University of Nottingham
Department Name: Div of Electrical Systems and Optics

Abstract

Transducers are devices that can convert electrical energy into mechanical energy and vice versa. They are widely used in non-destructive testing to generate acoustic signals in test materials and to detect changes in the acoustic signal as it travels enabling material properties to be determined. The application areas for transducers in non-destructive testing are diverse and range from locating cracks in metal structures to diagnosing disease in humans.

Transducers are typically made from single crystals such as quartz or ceramics. Recently it has been shown that a much wider range of materials can be used in transducers if they are miniaturised down to a nanometre scale. In fact, it has been shown that electrical energy can be converted to mechanical energy in biological membranes. Further, strategies to greatly increase the size of this effect have also been identified. These findings are very exciting as they pave the way for development of tiny transducers that could be used in the human body without posing any risk of toxicity, thus having tremendous potential for application in medicine. The work proposed in this Fellowship is centred on the development of nano-sized transducers made from phospholipids, which are the main type of fat found in membrane of biological cells.

A huge area of application for the nano-transducers proposed is in medical imaging which presents a number of challenges. In practice, the nano-transducers could be used to remotely probe tissue properties and used in an imaging system to aid the diagnosis of disease. There is also a growing need for new imaging systems capable of remotely studying cells and tissues in the body to support the development of emerging therapies that use human cells to treat currently incurable conditions, such as Parkinson's disease and spinal injury, as well as chronic conditions including diabetes and heart disease. The hope is that by introducing new healthy cells into the body they will help to restore the function of injured or diseased cells. To ensure these therapies have a positive effect it is important that the location and behaviour of introduced cells are tracked once in the body. This is a challenging problem which current technologies are struggling to address.

The work proposed in this Fellowship will address the above challenges. The approach that will be taken is different from other workers particularly as it will involve the development of transducers made from organic material. A major part of the proposed work will be designing and fabricating the nano-transducers. The phospholipids the nano-transducers will be composed of will be formed into bubbles called liposomes. Due to the natural link between the electrical and mechanical properties of liposomes it will be possible to use them as tiny acoustic sources. Strategies to increase the size of the acoustic signal produced will be developed based on modification of the liposome composition, shape and size. Another part of this Fellowship will be the development of a suitable imaging system using the nano-transducers that can be used to produce diagnostic images of the body. Also by controllably decorating the liposomes with specific biological molecules the nano-transducers will be able to target certain cell types enabling them to act as beacons to locate cells in the body. The final part of the work will be centred on demonstrating the capability of the new imaging system using tissue phantoms that mimic the human body. In particular, the ability to detect tumours, electrical activity in the brain and track cells used in therapy will be investigated. Overall, the success of this work will deliver a new medical imaging modality that could be implemented readily within clinical pathways at the point of care. This would have a significant impact on healthcare and enable new therapies to become available for clinical use and thus contribute to the health and wealth of society.

Planned Impact

Beneficiaries of research undertaken within this Fellowship include industry, patients and their support networks, and healthcare providers/funding agencies.

The technology developed in this Fellowship will support both the emerging regenerative medicine market and that of medical devices. In regenerative medicine non-toxic probes are required to enable selection of the most promising cells for use in treatment and monitor these cells once in the body and the development. Current probes such as quantum dots raise concerns about long term safety when used in the body so alternative methods are required. The alternative approach proposed within this Fellowship addresses one of several bottlenecks in regenerative medicine product translation. The probes developed also have application in the broader context of medical imaging, specifically by creating a new medical device to improve diagnosis of disease and functional imaging in a format compatible with current clinical pathways.

In addition, the research team assembled to deliver this research will gain a unique expertise in regenerative medicine, in vivo imaging and engineering combined with an excellent understanding of the needs of the regenerative medicine and medical device markets: an attractive skill set for an industry where, especially for regenerative medicine, there is a noted skills shortage.

Regenerative medicine offers patients suffering from currently incurable and chronic conditions such as Parkinson's disease, spinal injury and diabetes improved treatments and, potentially, a cure. Meanwhile portable medical devices for non-invasive, in vivo imaging offer the potential for rapid diagnosis at the point of care. The prospect of improved quality of life - emotionally, socially and financially - and life extension is of clear benefit to patients. There are also obvious benefits for a patient's support network - principally their family and friends - who no longer need to provide such intensive care and see loved ones suffer.

Medical devices for disease diagnosis at the point of care and in small satellite clinics that can be implemented into current clinical pathways will benefit healthcare providers. Further, common conditions can be targeted by regenerative medicine and has the potential to substantially reduce costs and hospital admission stays, especially when taking current statistics into account, for example:

* Diabetes accounts for 5% of all NHS expenditure (£3.5bn in 2006) and 10% of hospital in-patient costs. Every year 20% of the estimated 2.6 million people in the UK with diabetes will be admitted to hospital, usually for some incidental condition or complication. The complications of diabetes are numerous and deadly, and include amputation, heart disease, kidney failure and blindness. (www.policyexchange.org.uk and www.diabetes.nhs.uk)

* Heart disease cost the health care system in the UK around £14.4bn in 2006 with hospital care account for about 72% of these costs. The overall economic cost of heart disease - including healthcare costs, production losses from death and illness in those of working age and from the informal care of people with the disease - was estimated to be £30.7bn. (www.heartstats.org)

The timescale for delivering impact will be over the longer term. The technology is a long way from being suitable for uptake by industry but once developed is likely to be adopted quickly as it addresses a particular need. Health benefits and the additional associated economic benefits of improved health will be realised over a longer term due to regulatory approval and clinical adoption times.

Publications

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Related Projects

Project Reference Relationship Related To Start End Award Value
EP/J001953/1 01/10/2011 31/07/2015 £733,385
EP/J001953/2 Transfer EP/J001953/1 01/08/2015 31/03/2017 £289,011
 
Description Key findings to date include the demonstration of sound generation via application of pulsed electric fields to suspensions of liposomes thus demonstrating the principle of the nano-transducers. Further, experimental work has been undertaken to screen a range of liposome compositions to identify preparations that lead to enhanced sound generation. In particular, modifications to increase the membrane dipole potential have been made through the inclusion of cholesterol and transmembrane proteins in the liposomes as well as changes to the charge on the lipid head-group.
The most recent work has been based using pyrene labelled liposomes as contrast agents that produce an ultrasound modulated optical emission. The exposure of these liposomes to ultrasound can change the collision rate of the pyrene molecules and hence modulate the optical emission. In the current work, 100 nm sized liposomes composed of varying concentrations of pyrene-labelled phospholipids were investigated to identify a suitable liposome-based US contrast agent candidate. The fluorescence emission of the pyrene-labelled liposomes insonified by continuous US were studied. It has been observed that the excimer emission from 0.5 mol% pyrene-labelled liposome is US sensitive at pressures between 1.4 MPa and 2.7 MPa. This work will have application in high resolution, high contrast fluorescence imaging.
Exploitation Route This research will support the medical device industry and help maintain the UK's world leading capability in medical imaging, which is of key national importance due to the significant inward investment this attracts. Medical devices for disease diagnosis at the point of care and in small satellite clinics that can be implemented into current clinical pathways will be of significant benefit to healthcare providers. Further, relatively common conditions can be targeted by regenerative medicine which has the potential to substantially reduce costs and hospital admission stays. Commercial opportunities are likely to arise for applications of the nano-transducers in medical diagnostics and in validation of regenerative therapies. Potential partners to take these forward will be identified through presentations (and follow-up meetings), the applicant's and colleagues' own contacts, the Fellowship's advisory group and the University's Technology Transfer Office (TTO). Potential funding for follow-on activity includes INHR i4i programme, TSB Technology Programme, EU FP7/8, direct industry funding, and EPSRC and BBSRC for more basic research proposals.

The need for protection of intellectual property will be assessed in consultation with the TTO which will also assist with the development and implementation of longer-term exploitation strategies.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description ERC Consolidator Grant
Amount € 2,400,000 (EUR)
Organisation European Research Council (ERC) 
Sector Public
Country Belgium
Start 07/2016 
End 06/2021
 
Description Imaging Technology Development for the 3Rs
Amount £347,834 (GBP)
Funding ID NC/L00187X/1 
Organisation National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2015 
End 04/2017
 
Description The Royal Society Research Grant Award
Amount £15,000 (GBP)
Funding ID RG130755 
Organisation The Royal Society 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2014 
End 03/2015
 
Description BBC Radio Nottingham 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Interviewed live on BBC Radio Nottingham to describe the research that will be carried out as part of this EPSRC Career Acceleration Fellowship

I was contacted by the Nottingham Post Newspaper and they ran an article in their paper about the research project.
Year(s) Of Engagement Activity 2011,2012