Nanojuice: drinkable nanoparticles for studying the gut
Over the past few days, my news and social media streams have been inundated by articles on “nanojuice”. The “juice” – developed by researchers at the University of Buffalo and published in the journal Nature Nanotechnology – is a suspension of light-absorbing nanoparticles which, when drunk (and only mice have had this privilege so far), allow an unprecedented level of real-time imaging of the small intestine. It also presents an unusual series of safety challenges as the particles are designed to be intentionally ingested.
The nanojuice particles are around 20 nm in diameter, and are formed from naphthalcyanines – chemicals that highly absorb specific wavelengths of light. Using stable nanoparticles enabled the researchers to ensure the naphthalcyanines could be ingested at sufficiently high concentrations to be effective and get into all the nooks and crannies of the intestine, without passing through the intestinal wall and entering into the body.
After being ingested, the “patients'” small intestine is illuminated with pulses of laser light. Nanoparticles in the beam absorb the pulses, and as they heat and cool, they emit sound waves. By monitoring these sound waves, it’s possible to map out the concentration of nanoparticles in the laser beam, and to create a near real-time image of the small intestine. The technique is, not surprisingly, referred to as photoacoustic imaging.
Safety studies
If the nanojuice technology makes the transition from the experimental stage through human trials, it could provide unique insights into the understanding, treatment and prevention of bowel conditions and diseases that in many cases are not well understood. However, as the technology involves the intentional ingestion of nanoparticles, there’s likely to be close scrutiny paid to the toxicity and potential health impacts of these particles in the gut before it becomes widely available.
Realizing this, the researchers carried out a number of tests to evaluate the safety of the naphthalcyanine nanoparticles.
Toxicity to the cells lining the gut was evaluated in cell cultures using Caco-2 cells – these are standard test cells for exploring gastrointestinal tract toxicity. The researchers measured the percentage of cells that died at increasing concentrations of nanojuice. They also carried out similar experiments with the dye Methylene Blue (not administered as a nanoparticle) as a comparison. Concentrations of either the nanoparticles or the Methylene Blue were characterized by their optical density – how much light at a specific wavelength they absorbed.
At an optical density of 1, 50% of cells exposed to the Methylene Blue died, and at an optical density of 100, 100% of the cells were dead. In contrast, there was no significant cell death observed with the nanojuice up to an optical density of 100.
The researchers went on to expose mice to a concentration of nanojuce with an optical density of 100 (equivalent to 3.42 mg of material). All of the administered material was excreted in the animals’ feces, indicating that it was not absorbed through the gut wall, or retained in the gut for a significant length of time. In contrast, the Methylene Blue was readily absorbed into the bodies of the mice.
Finally, researchers exposed mice to a concentration of nanojuice with an optical density of 50,000 per kilogram body weight – ten times the dose that would be used in intestinal imaging. Over a two-week period, there were no indications of toxicity: The animals behaved normally, and subsequent tissue samples showed no signs of adverse effects.
From lab to gut
These results are encouraging – they indicate that the naphthalcyanine nanoparticles pass through the guts of mice without passing across the gut wall and into the body, and without causing harm. It is frustrating that data are presented in terms of optical density rather than mass concentration, as this makes it difficult to compare the data with other toxicology studies. There is also a need for some caution as human trials are considered, as there is still a lot that is unknown about subtler interactions between the gut and nanoparticles – including their interaction with the gut’s immune system.
That said, these early data indicate that this could be a highly effective tool for exploring, diagnosing and treating illnesses of the small intestine which continue to challenge the medical community.
More information
Image: The combination of “nanojuice” and photoacoustic tomography illuminates the intestine of a mouse. (Credit: Jonathan Lovell)
Paper: Zhang et al. (2014) Non-invasive multimodal functional imaging of the intestine with frozen micellar naphthalocyanines. Nature Nanotechnology DOI: 10.1038/NNANO.2014.130
Supplementary material (PDF) http://www.nature.com/nnano/journal/vaop/ncurrent/extref/nnano.2014.130-s1.pdf
FDA information on nanotechnology and regulatory approaches to nanotechnology-based products: http://www.fda.gov/ScienceResearch/SpecialTopics/Nanotechnology/default.htm
Update July 13: Added section headings