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New discovery reveals fate of nanoparticles in human cells

Scientists funded by the Biotechnology and Biological Sciences Research Council (BBSRC) have uncovered what happens to biomimetic nanoparticles when they enter human cells.

They found that the important proteins that make up the outer layer of these nanoparticles are degraded by an enzyme called cathepsin L. Scientists now have to take this phenomenon into account and overcome this process to ensure the exciting field of nanomedicine can progress. The research is published today (22 September) in ACS Nano.

Dr Raphaël Lévy, a BBSRC David Phillips Fellow at the University of Liverpool and lead researcher on the project said: “We’ve known for some time that nanoparticles are taken into cells and there have been experiments done to establish their final destinations, but we didn’t know until now what state they are in by the time they get there.”

In most biological applications, nanoparticles are coated with a layer of molecules, often proteins, which determine the use of nanoparticles when they enter cells. The researchers have confirmed, in a wide range of cells, that nanoparticles are taken into a region called the endosome, where this essential coating is degraded by cathepsin L.

Dr Violaine Sée, also a BBSRC David Phillips Fellow at the University of Liverpool, and joint corresponding author, added: “One of the promising applications of nanoparticles in medicine is to use them as a method to deliver therapeutic protein molecules inside cells. For these biological therapies to be effective the proteins have to be maintained with high integrity and unfortunately we have seen this compromised by the degrading action of cathepsin L.”

The design of any intracellular nanodevice must now take into account the possibility of cathepsin L degradation and either bypass the endosome area all together or have some built-in inhibition of the enzyme.

Dr Lévy continued: “The methods we have developed will help with this as we can now measure the location and the state of the nanoparticle quickly and quantitatively.”

Professor Douglas Kell, BBSRC Chief Executive said: “Nanotechnology is an interesting area that has the potential to push all sorts of technological boundaries. There is promise of some useful applications in biology and we’ve already seen some excellent results with the development of nanomagnetic technology to guide therapeutic proteins and DNA to specific sites to treat tumours, for example. Fundamental bioscience research such as this, helps drive forward nanomedicine to ensure it has a real impact on health and wellbeing in the future.”

About the University of Liverpool
The University of Liverpool is a member of the Russell Group of leading research-intensive institutions in the UK. It attracts collaborative and contract research commissions from a wide range of national and international organisations valued at more than £93 million annually.
The Biotechnology and Biological Sciences Research Council (BBSRC) is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £450 million in a wide range of research that makes a significant contribution to the quality of life for UK citizens and supports a number of important industrial stakeholders including the agriculture, food, chemical, healthcare and pharmaceutical sectors. BBSRC carries out its mission by funding internationally competitive research, providing training in the biosciences, fostering opportunities for knowledge transfer and innovation and promoting interaction with the public and other stakeholders on issues of scientific interest in universities, centres and institutes.

The Babraham Institute, Institute for Animal Health, Institute of Food Research, John Innes Centre and Rothamsted Research are Institutes of BBSRC. The Institutes conduct long-term, mission-oriented research using specialist facilities. They have strong interactions with industry, Government departments and other end-users of their research.

Nancy Mendoza | EurekAlert!
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