Positively charged gold nanoparticles can penetrate deep into cell membranes while negatively charged particles do not enter the cell wall at all, but instead prevent it breaking down under certain conditions. This new result, from researchers working in France, the US and Australia, could help design nanoparticles for biomedical applications such as drug delivery and anti-cancer treatments.

Gold nanoparticles make particularly good drug-delivery vehicles thanks to the fact that they can be loaded with molecules like anti-cancer dugs. Their surfaces can also be easily modified with antibodies to target specific receptors on tumour cells.

The particles can also be made biocompatible and generate heat when illuminated with light. This heat can then be used to locally destroy cancer cells without harming surrounding healthy tissue. Gold nanoparticles are ideal for such "photothermal therapy" because their optical properties can be tuned in the near-infrared part of the electromagnetic spectrum – the wavelengths at which light most deeply penetrates biological tissue.

Researchers now know that a variety of factors, such as a nanoparticle's shape, size and surface charge, affect the way that it interacts with cells. In the new work, the researchers, who are based at the Institut Laue-Langevin in France, the University of Chicago in the US and the Australian Nuclear Science and Technology Organization, looked at how gold nanoparticles affect the structure of a cell membrane – the first barrier that any foreign body has to penetrate to enter a living organism.

Ideal model cell membrane

Real cell membranes are very complex structures and consist of an asymmetric lipid bilayer comprising several types of lipids with embedded proteins. Producing such complex structures in the lab is difficult so the researchers studied a simplified membrane made of just one kind of lipid (1,2 distearoyl-sn-glycero-3-phosphocholine). In the experiments, two double layers of lipid molecules made to "float" about 20–30 angstroms on top of each other were used.

The team working at the ILL employed a technique known as "neutron reflectometry", which is able to characterize layered structures deposited on a flat surface at resolutions of just a fraction of a nanometre. Neutrons themselves are ideal for studying buried interfaces because they interact very weakly with matter as the neutrons themselves are uncharged. They can thus penetrate successive sample strata very easily.

Membrane interface structure

The scientists looked at how 2 nm diameter gold nanoparticles, which either had cationic or anionic groups added to their surface, interacted with the model cell membranes. They began by firing a beam of neutrons at the samples that hit the nanoparticle-surface group interface at a particular grazing angle. They then measured the intensity of the reflected radiation as a function of this angle – something that provided them with information about the structure of the interface in terms of thickness, roughness and density in the presence of the two differently charged nanoparticles.

"We found that the surface charge on a nanoparticle does indeed play a significant role in determining its interaction with the cell membranes we studied," team member Giovanna Fragneto told physicsworld.com. "Cationic nanoparticles pass straight through the membrane, embedding themselves deeply within the floating bilayer and destabilizing the entire membrane structure enough to completely destroy the cell at higher concentrations. In contrast, anionic nanoparticles do not penetrate the lipid membrane at all but rather hinder membrane decomposition at given concentrations, helping it withstand extreme conditions such as elevated pH that would otherwise significantly destabilize it."

"That these nanoparticles can attack outer cell walls is both concerning from a general health point of view but also potentially exciting in terms of future medical treatment," added team member Marco Maccarini.

The team says that it would now like to look at mixtures of two or more different lipid molecules to make model membranes that even better resemble real ones.

"Understanding the interaction between nanoparticles and cell membranes has two-fold importance," says team member Sabina Tatur. "On one hand, it will allow us to be more aware of potential risks for human health. And on the other, it will help us to develop nanoparticles that could be used for specific biotechnology applications, such as drug-delivery systems, cancer therapies and biosensing."

The researchers published their work in Langmuir.