Dynamic PET/CT imaging and tissue distribution of radio-labelled fresh GO ([64Cu]-f-GO-thin), aged GO ([64Cu]-f-GO-thick) and a control ([64Cu]-EDTA). (A) Whole body PET/CT images of mice injected intravenously with fresh GO (top) and aged GO (bottom) at different time points (1, 3.5, 24 h); (B) Time activity curves of major organs of mice injected with fresh GO, aged GO and control; (C) Whole body PET/CT images of a mouse injected intravenously with a control sample showing almost complete excretion and no tissue accumulation after 3 h.
Dynamic PET/CT imaging and tissue distribution of radio-labelled fresh GO ([64Cu]-f-GO-thin), aged GO ([64Cu]-f-GO-thick) and a control ([64Cu]-EDTA). (A) Whole body PET/CT images of mice injected intravenously with fresh GO (top) and aged GO (bottom) at different time points (1, 3.5, 24 h); (B) Time activity curves of major organs of mice injected with fresh GO, aged GO and control; (C) Whole body PET/CT images of a mouse injected intravenously with a control sample showing almost complete excretion and no tissue accumulation after 3 h.

According to new research, freshly made graphene oxide sheets – fabricated by oxidizing graphene to cover the surface in oxygen groups – are excreted quickly and efficiently from the body [Jasim et al., Applied Materials Today 4 (2016) 24]. In fact, over 75% of graphene oxide (or GO) sheets injected into mice were eliminated from the body through the kidneys in the urine within 24 hours.

The unique properties of graphene promise many novel applications, especially in biomedicine where its large surface area, high strength, and flexibility could be an boon for drug delivery or as a contrast agent for diagnostic imaging techniques like PET (positron emission tomography) scanning. One of the key properties of such agents is fast excretion from the body.

But the team from the University of Manchester in the UK and the CNRS Institut de Biologie Moléculaire et Cellulaire in Strasbourg, France have found that over time GO forms into thicker stacks, which affects its behavior in the body. 

“Aging of thin functionalized GO material leads to re-stacking of the flakes that results in materials of increased thickness without altering their lateral dimension,” explain Dhifaf A. Jasim and Kostas Kostarelos from the University of Manchester.

After radio-labeling freshly made and aged GO samples – which had been kept in the lab for 18 months, the researchers tracked the progress of each type immediately after injection into mice and again 30 minutes, 3 hours and 24 hours later using PET imaging. 

“A significantly larger fraction of the thicker GO sheet (47.5% of the injected dose) remain in the body 24 hours after administration, mainly in the spleen and liver,” say Jasim and Kostarelos. “By contrast, the thinner GO sheets (76.9%) were excreted in the urine.”

The researchers believe the variation is down to the difference in thickness of the GO stacks. When fresh, the GO stacks are just 4-8 nm thick. But the aged GO stacks are up to four times thicker (around 40-50 nm thick). 

Inside the body, this difference has a profound effect on excretion. The freshly made GO stacks are thinner and more flexible, making it easier to penetrate the blood filtration barrier and get into the urine.

Conversely, the barrier prevents larger particles such as the aged GO getting into the urine. The aged GO is more rigid and cannot squeeze through the barrier so easily. So the aged GO stacks accumulate in the liver and spleen to a much larger degree.

“GO holds great potential for biomedical applications,” say Jasim and Kostarelos. “But understanding the importance of GO characteristics is critically important. Once we learn the basics, we should be able to design more sophisticated 2D constructs.”