Neutrons reveal potential dangers of pharma’s golden bullet

Gold nanoparticles are projected to be the ‘magic bullet’ of drug delivery, but scientists working at the Institut Laue-Laugevin have revealed the potential dangers of the tiny particles at high concentrations.

The growing use of nanoparticles in medical research comes from the major challenge to find drug delivery agents that can target and penetrate cells to transport drugs directly inside the affected tissue.

“The very very small size of gold nanoparticles is important because it allows them to interact and penetrate cell membranes,” said Marco Maccarini who was involved in the research.

But at present we don’t understand in any detail the interaction mechanisms between nanoparticles and cell membranes. All that is known is that there is a complex set of parameters that influence this interaction and these include the nanoparticles’ shape, size, composition and charge.

A systematic study that shows how the interaction depends on these parameters at a molecular level has up until now been missing.

So to start to address this, the researchers used ILL’s neutrons and world-leading neutron scattering instruments to investigate the physical changes undergone by cell membranes as they come into contact with gold nanoparticles that have different charges.

The team used gold nanoparticles 2 nm in diameter that had either cationic (positively charged) or anionic (negatively charged) groups added to their surface and an artificial lipid membrane to mimic a real cell membrane.

“We used a Langmuir-Trough to make very thin layers of lipid molecules in solution. We then applied the gold nanoparticles of various charges and used neutron reflectrometry to gauge their interactions,” Maccarini told Laboratory News. “Neutrons are an ideal tool for studying biological materials because we can visualise detailed structures of molecules.”

The researchers discovered that nanoparticle surface charge plays a significant role in determining their interaction with cell membranes. Cationic nanoparticles pass straight through the lipid membrane and embed themselves deeply within the floating bilayers, destabilising the entire membrane structure sufficiently to completely destroy the cell at higher concentrations. In contrast, anionic nanoparticles didn’t penetrate the lipid membrane at all.

“Our research shows the potential risks of the premature use of nanoparticles in everyday goods before all aspects of their safety have been defined and considered. Nanoparticles are indeed promising candidates for countless exciting applications – but only if they are shown to be harmless to health and the environment,” said team member Dr Sabina Tatur.