Anton Korenevski was doing laboratory work one night as part of a study into how bacteria stick to surfaces when he spotted something unusual. A post-doctoral researcher at the University of Guelph, Korenevski had just performed a complex chemical procedure and noticed what project leader John Dutcher describes as “a waste product that looked kind of cool.”
The nanosized material — bacteria poop, if you like — had opalescent properties, meaning it scattered light in different colours and from different directions. “Instead of throwing it away, Anton decided to keep it and find out what it was,” recalls Dutcher, director of the university’s nanoscience program and Canada Research Chair in Soft Matter and Biological Physics. Using an atomic force microscope, they learned that the mysterious particles were all the same size and perfectly round. They didn’t know what the material was made of, nor did they know what could be done with it. But their gut feeling was that it was a potentially significant finding, so they obtained some proof-of-principle funding and began a more thorough investigation. “Here was a chance to take a new material and really evaluate its promise as a technology,” Dutcher says.
That was back in 2006. Nine years later, what began as a hunch has developed into a massive market opportunity for Mirexus Biotechnologies, a University of Guelph spinoff that counts Dutcher as its chairman and Korenevski as chief scientist. The naturally occurring material they investigated — since branded Phytospherix — proved to have a powerful combination of properties, from being nontoxic and biodegradable to highly soluble and uniform in size. It also has an incredible ability to retain moisture. Translation: for a wide range of commercial applications it’s safer and better than other nanoparticles on the market.
Given this, it’s no surprise that makers of personal care products, specialty foods and pharmaceuticals, among others, are watching Mirexus’s progress closely. Dogged by health and environmental concerns around their use of nanomaterials, companies that rely on these particles have grown more eager to find less controversial alternatives. Just as remarkable, however, is how chemically unremarkable the Mirexus particles turned out to be. They’re just nanosized sugar balls, or more precisely a polysaccharide called phytoglycogen, a plant-based form of glycogen. Animals and plants naturally produce and store glycogen as an energy source. “It’s even edible,” says Dutcher, explaining how Phytospherix can be labelled non-toxic. “Glycogen is already found in human bodies,” says Emily Cranston, assistant professor with McMaster University’s department of chemical engineering. “That’s why there’s no chance of having a reaction to it.”
Noticeably different is that this polysaccharide has a unique spherical structure, which begins with a “seed” molecule that grows tree-like branches at regular intervals with assistance from enzymes. (Synthetically produced molecules called dendrimers form in a similar way.) “The cool thing about the dendrimer aspect is that it leads to self-limited growth,” Dutcher explains. “They grow and branch and grow and branch until there’s no room for the enzymes to get in. That leads to particles that are all the same size, naturally.”
Mirexus’s phytoglycogen nanoparticles, isolated and extracted from corn, have a structure similar to synthetic dendrimers, seen here. It starts with a “seed” molecule that grows through the addition of linear chains that branch out at regular intervals, resulting in an exponential increase in the density of the glucose as the molecule grows. The density gets so high that branching is no longer possible and the molecule’s growth comes to a halt. It is this final limitation that keeps the particles uniform in size.
Mirexus’s particles are currently 80 nanometres in diameter, meaning it would take 80,000 of them in a row to equal the width of a human hair. Anything under 100 nanometers gets itself the “nano” label. Being the same size means the particles are monodisperse, a property not found in most natural nanomaterials and which are expensive to produce in synthetic form. Dutcher says monodisperity is important because a particle’s ability to penetrate a cell depends greatly on its size. Having certainty of size makes it easier to predict how a particle will behave around, or be accepted by, living cells, such as when used to target the delivery of cancer drugs. For example, when cancer cells grow they stimulate the growth of new blood vessels, which create gaps between the cells that are larger than those found between healthy cells. A drug-carrying nanoparticle small enough to travel between cancer cells but too big to get between healthy cells would eliminate the carpet-bombing done through conventional chemotherapy treatment. “I’m really excited by what they’re doing,” says Cranston, who has been following the work of Dutcher’s team and is encouraged by their progress. “There are very few materials out there that are sustainable, non-toxic and nano, so this has huge potential.”
It’s difficult to question the seemingly endless benefits nanotechnology can deliver. Nanosized particles, created through modification of materials at the molecular level, are increasingly used to make polymer composites stronger, lighter and substantially more durable, helping improve the performance of everything from baseball bats to automobile parts. Such particles can turn materials into better insulators or conductors, improve the look, feel and performance of cosmetic products, help keep food from spoiling, and prevent fabric from wrinkling and becoming smelly. They also make exceptionally good coatings, whether providing scratch-resistance to sunglasses, reducing wear on machine parts, or enhancing the light-absorbing ability of solar modules. “Nanotechnologies are hailed by many as the next industrial revolution,” states the Woodrow Wilson International Center for Scholars, which in 2005 established the Project on Emerging Nanotechnologies (PEN) to act as a kind of public watchdog as nanotechnology advances and gains more market momentum. By the end of 2013, PEN had identified more than 1,600 consumer products containing nanomaterials. Given lofty market forecasts, there’s little doubt that number has since climbed significantly.
Market research publisher Global Industry Analysts (GIA) estimated last fall that the global market for nanotechnology will reach US $3.5 trillion. “Increasing production of nanomaterials, declining prices and rapid commercialization are driving growth in the market,” GIA found. “Future growth in the market will be primarily driven by pharmaceutical, healthcare and food industries.”
Along with the rapidly growing use of nanotech, however, has come a wave of concern. What will its impact be on human health over the long run? How will nanoparticles affect ecosystems? Is there potential for irreparable harm? “We don’t really know,” says Dutcher. “Humans have a tendency to start using something before it’s fully understood. Sometimes that’s bad.”
For Mirexus, the controversy is fortuitous. The company has a relatively benign innovation emerging at a time when the long-term use of nanotechnology is being seriously questioned. In study after study, red flags keep popping up. In a November 2014 study conducted at the Technion-Israel Institute of Technology, silicon-based nanoparticles exposed to mouse arterial cells caused lesions and hastened the onset of atherosclerosis. The findings suggest a possible occupational health risk for workers in high-tech manufacturing industries.
John Dutcher, chair of Mirexus Biotechnologies, a University of Guelph spinoff company that developed the nontoxic and biodegradable nanomaterial Phytospherix. Photo credit: Martin Schwalbe
In a report recently published online in Environmental Engineering Science, researchers from the University of California documented the impact three nanoparticles had on microorganisms typically present inside an individual’s gut, in this case, a model of a human colon.
Cerium dioxide, titanium dioxide and zinc oxide were specifically studied because of their prevalence in a range of products, including cosmetics, toothpaste and sunscreen. The researchers observed “significant changes” to the microbial community’s development and behaviour inside the colon model, “which may be related to overall health effects.”
The tricky thing with nanoparticles is that they’re just super small versions of materials that are well understood and generally considered safe. But when they are engineered at the nanoscale, they start to behave in ways we don’t fully understand. They can become more chemically reactive. They can penetrate and interact with cells, pass through membranes like the blood-brain barrier and enter vital organs, bone and nerves. Another University of California study, this one in 2009, observed DNA damage and “genetic instability” in mice that drank water tainted by particles of normally inert titanium dioxide.
Food isn’t the only concern. So, too, is what we apply to our skin. Sunscreen contains titanium dioxide or zinc dioxide nanoparticles, which act as blockers of ultraviolet radiation. All sorts of cosmetics use nanomaterials to enhance colour, alter transparency levels and improve solubility. But the particles can also penetrate the skin, or wash off and ultimately find their way into rivers, lakes and ocean waters.
An April study published in Environmental Science and Technology found that zinc oxide nanoparticles weakened the embryos of sea urchins, making them more vulnerable to other contaminants. Considering all the potential benefits and risks, one overarching question dominates the debate over nanomaterials: are the trade-offs acceptable?
The hope for Mirexus is that such trade-offs won’t be necessary, at least in the markets it plans to target. “We can replace things like petroleum-based products or inorganic compounds that would have all these unwanted properties but we also offer performance enhancements as well,” says Dutcher.
It didn’t take long to realize that bacteria poop wasn’t an economical way to produce large volumes of the glycogen-based nanoparticles, despite experimentation with different fermentation techniques. Fortunately, by 2008 the Mirexus team had isolated the same polysaccharide structure inside corn and began work with the Ontario Ministry of Agriculture, Food and Rural Affairs to identify varieties of corn that had the highest glycogen-to-starch ratio.
It turns out that sweet corn, the kind Canadians roast on the barbecue every summer, is one of the best at producing the uniquely structured phytoglycogen particles. It raises a point that Dutcher regularly makes: it’s the plant that naturally manufactures the miracle nanoparticles, not Mirexus. The specific challenge Dutcher’s team had was in designing a process to isolate and remove the particles in large volumes, at scale, without destroying their unique structures and without using chemicals. That’s the innovation they bring to the table. “We gently extract them and purify them while preserving their very special properties,” Dutcher says.
Having figured this out, Mirexus researchers spent the next few years documenting the many unique properties of the material and identifying markets where application could prove beneficial. By 2013, Dutcher felt the company was ready to start commercializing its Phytospherix particles. At the same time, he recognized his own limitations as a scientist. Mirexus’s patents were in good shape, but the company really didn’t have a business plan. This realization kick-started the search for a CEO who could raise capital and take the venture to a new level.
Phil Whiting, previously the CEO of solar thermal energy company EnerWorks, turned out to be the right fit. Whiting first heard about the work Dutcher’s team was doing at a clean technology conference in Toronto and was intrigued, especially since he had just moved to Guelph. Whiting was so excited about Mirexus’s potential that he worked for the first half-year without pay, during which time he began the hunt for investors. It proved fruitful, leading to a $350,000 round of angel investment from Toronto-based GreenSky Capital and $150,000 from GreenCentre Canada in Kingston, Ont. In April, Mirexus closed a $4.5 million deal with Barbados-based Goddard Enterprises, which owns and operates companies in the Caribbean. Turns out the CEO of Goddard, Tony Ali, previously worked with Whiting as vice-president of sales at EnerWorks. “We became their first venture investment,” says Whiting, who calls the deal serendipitous. Now strategic interest in Mirexus is starting to catch on, in part because of the company’s decision to exhibit at the In-Cosmetics Barcelona show next April. “The message we got back from the market is that in the cosmetics space there’s a lot of interest in natural materials and ingredients like ours that also offer superior properties,” Whiting says.
Since then, a large Japanese company that makes big quantities of hyaluronic acid — the gold standard ingredient in high-end moisturizers — committed to invest after testing the ability of Mirexus’s nanoparticles to retain moisture. “They compared our material to the acid and we blew it out of water,” says Whiting, who admits it was a huge boost of confidence.
The market for sports drinks that can slowly release sugars and nutrients is also being targeted in the near-term, as well as sunscreens. Dutcher says he can’t entirely explain why but the company’s nanoparticles boost the Sun Protection Factor of sunscreen and makes it last longer. “It somehow protects the photoactive compound within the sunscreen, meaning you don’t have to reapply it as often,” he says.
To pursue applications around drug delivery, the company created a subsidiary this past May called Mirexus Biomedical, which will also explore opportunities around vaccine enhancement and medical imaging. The customer pipeline is growing and Mirexus is working with hundreds of companies from across industries. “Our biggest hope — and our biggest fear — is that we’ll get a big order,” says Dutcher, half joking. “This means having the whole manufacturing process nailed down.”
And a steady supply of Ontario-grown sweet corn — preferably organic.