Gold nanoparticles are well known as a drug-delivery platform that can successfully permeate cell membranes, taking their payloads directly to where they are needed. Now, MIT researchers have determined just how the nanoparticles are able to achieve this.
Gold nanoparticles coated with amphiphilic polymers can fuse with cell membranes, allowing them to pass into cells without damaging them. Image credit: Reid Van Lehn/MIT.
In 2008, it was discovered that gold nanoparticles, coated with a specific polymer, were highly effective at penetrating biological cells. This platform makes it much easier to deliver chemicals such as drugs or nutrients, or even more complex systems like diagnostic sensors, into the heart of the cells, when they would normally be rejected or taken up very slowly.
Until recently, however, it was not clear why this worked. Now, researchers from MIT, along with a team at EPL in Switzerland, have fully described the process by which the nanoparticles pass through cell membranes without damaging the cell, and have also determined the maximum size for particles that are able to do this. The work has been published in Nano Letters in August 2013.
The core of the discovery is that the coated nanoparticles actually fully fuse with the lipid bilayers which make up the cell membrane.
This is possible because of the amphiphilic nature of the material used to coat the gold nanoparticles - typically monolayers of hydrophobic polymer chains, functionalized with hydrophilic chemical groups at their ends.
This structure is broadly similar to that of the lipids which make up the cell walls, making the interior of the barrier a very stable environment for the coated nanoparticles.
Because of this similarity, the gold nanoparticles can be absorbed into the cell membrane without requiring any energy to push them through, and the membrane closes seamlessly behind them without letting anything else slip in behind them.
This is in contrast to uncoated gold nanoparticles, which actively damage the cell membrane when they pass through it, causing cell death. Many other peptides and other chemicals either have this same damaging effect, or cannot pass through the barrier at all.
This deeper understanding of the mechanism which allows nanoparticles to penetrate biological cells with such ease will make research into practical applications of the phenomenon a good deal simpler. Altering the coating used to target certain types of cell, or adding on functional groups to deliver additional functionality, will be much simpler now that the limiting parameters have been more clearly defined.