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.

The proteins that make up the outer layer of these nanoparticles are degraded by an enzyme called cathepsin L, they have found. They now have to overcome this process to ensure the progress of nanomedicine. The research is published in ACS Nano.

Dr Raphael Levy, 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 See, 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 or have some built-in inhibition of the enzyme.