03-12 oxygen mask

[Image above] A U.S. Air Force airman demonstrates how to breathe from an oxygen mask. A recent study investigating the health effects of inhaling graphene oxide used a similar mask to expose volunteers to the nanomaterial. Credit: Eugene Oliver, U.S. Air Force

As the possibilities attainable with nanoscience start to materialize in more and more industrial sectors, concerns about the health risks of working with nanomaterials are becoming a big topic of discussion.

Nanomaterials have a larger surface area-to-volume ratio than their bulk counterparts, which makes them more reactive to their surroundings. This reactivity is beneficial when used in sensing or catalytic applications, for example, but it can trigger harmful biological reactions as well, such as inflammatory responses, oxidative stress, and even cell death.

Also, the small size of nanoparticles allows them to permeate the physiological barriers of living organisms more easily. Taken together with their enhanced reactivity, nanoparticles can enter the human body through the lung, intestinal tract, or skin and initiate damaging internal responses.

Because of the possible severity of these responses, governing bodies may preemptively initiate policy changes even when cytotoxicity is uncertain. For example, the European Union’s decision to ban the use of titanium dioxide as a food additive.

To date, studies on the health risks of nanomaterials have focused mainly on zinc oxide, silicon dioxide, titanium dioxide, silver, and carbon nanotubes. But as other nanomaterials grow their market share, it is important that their potential biological impacts be properly assessed.

In a recent open-access paper, researchers led by the Universities of Edinburgh and Manchester in the United Kingdom conducted the first-in-human clinical trial on inhaled graphene oxide nanosheets.

Graphene oxide has gained a lot of attention recently in biomedical settings due to its hydrophilicity and reasonable colloidal stability plus compatibility with blood cells. However, the toxicological data available for graphene oxide is limited and inconsistent due to the many different sources of this material and its variability in dimensions and chemical properties.

In the new study, the researchers synthesized highly purified graphene oxide nanosheets using a modified Hummers’ method, i.e., a chemical process that involves adding potassium permanganate to a solution of graphite, sodium nitrate, and sulfuric acid. They sized the nanosheets based on samples from previous pre-clinical studies on rodents that demonstrated no acute or longitudinal adverse effects.

Fourteen volunteers inhaled either the graphene oxide or filtered air for two hours under carefully controlled conditions, and they did so at three separate times spaced two weeks apart. The researchers measured heart rate, blood pressure, and lung function and took blood from each volunteer before and after each exposure. Vital signs were monitored up to four hours after exposure ended.

The data showed no acute changes in respiratory or cardiovascular function, nor systemic inflammation, in any of the volunteers. There was a slight suggestion that graphene oxide may influence the way the blood clots, but the researchers stress that this effect was very small.

The researchers acknowledge that higher concentrations or longer durations of graphene oxide exposure may result in physiological effects. But for comparison, their previous studies on diesel exhaust exposure using similar concentrations were accompanied by cardiovascular dysfunction in that same amount of time (see here and here).

In a University of Edinburgh press release, senior author Mark Miller, research scientist in the Center for Cardiovascular Science at the University of Edinburgh, notes that this clinical trial is a “huge” step forward in understanding how graphene may affect the human body.

“With careful design we can safely make the most of nanotechnology,” he says.

The open-access paper, published in Nature Nanotechnology, is “First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses” (DOI: 10.1038/s41565-023-01572-3).