3D liver model to test nanoparticle safety

Baby formula, doughnuts and sunscreen are not things that would normally strike fear in the average person, but for PhD student Dipesh Khanal, it’s a different story.

Dipesh is investigating the safety of nanoparticles, which are used in many processed foods, cosmetics and medications, and have been linked to cell damage.

“Nanoparticles are so small; they can infiltrate the cells and damage proteins. There is so much work going into furthering nanotechnology, but we still aren’t sure about its long-term impact on health,” Dipesh said. 

“There’s evidence that exposure to nanoparticles could be linked to diseases such as Alzheimer’s, fibrosis and even cancer.”

Originally from Nepal, Dipesh joined the University in 2014 on an Australia Award scholarship. He is studying the effect of nanoparticles on liver cells, which is where the majority of nanoparticles end up as the body tries to excrete them.

He has devised a cheap and efficient way to conduct the research without the use of animals – a 3D liver model that mimics the in vivo environment.

In fact, this 3D liver model has earned Dipesh the University’s award for reduction in the use of animals in research.

The model involves growing liver cells in a petri dish before adding magnetising properties and using specialised techniques in order for the cluster of cells to grow in on itself in a doughnut-like shape.

“Cells don’t like gaps, so they will communicate with each other and try to migrate and close in the gap, but they can’t if they are unhealthy,” Dipesh said.

“We developed a software program linked to an iPod that videos the cells over a 48-hour period. After adding nanoparticles to the cells, we could measure whether the cells could still ‘close the gaps’ and remain healthy. If they couldn’t we knew they were unhealthy and affected by the nanoparticles.”

Dipesh said the discoveries were further confirmed through detailed measurements using the Faculty of Pharmacy’s unique nano-bio-characterisation facility, which houses the most powerful tools available for nano characterisation.

“By measuring the gap in the ring (cells printed into doughnut shape), we could estimate the toxicity and level of damage caused by the nanoparticles in different concentrations.”

Dipesh tested nanodiamond particles, which are a commonly used drug delivery agent and are regarded as one of the safest biocompatible materials.

“We thought if we could show that the ‘safest’ nanoparticles are in fact harming cells, then it would call into question other nanoparticles such as titanium dioxide, which is widely used in food colouring and sunscreen.”

The tests did indeed show that liver cancer cells were adversely affected by the nanoparticles, with cell death and loss of cell functionality recorded. Dipesh said the next step is to see what they are doing to healthy liver cells.

Now in his third year of a PhD at the University under the supervision of Dr Wojtek Chrzanowski, Dipesh said he is excited to come to the lab every day, sometimes even staying overnight to monitor his experiments.

“I really enjoy the environment, the freedom, the supervisors and the colleagues – they entertain your ideas. It’s exciting. Every day you come to the lab, you do your research, you find new things.”

Dipesh’s ultimate goal is to decrease nano-specific risks in our food, while paving the way for a more sustainable nanotechnology industry. 

“Each day, a child can consume up to 35mg of nanoparticles – that’s trillions of nanoparticles that go into their body.”

“It’s imperative we find out the concentrations in which nanoparticles are safe.”