Amanda Engler talks about tiny infection-fighters
Imagine microscopic structures racing through your bloodstream like the X-wing fighters of the Star Wars films. But these aren't attacking an evil empire, they're targeting bacteria that are all but immune to conventional antibiotics. And they're not products of a rebel alliance either, but of IBM researchers. Welcome to the world of nanomedicine.
IBM's entry into the field was serendipitous, says Amanda Engler, a post-doctoral researcher on the nanomedicine team. Another team member, James Hedrick, was using nanostructures in the production of semiconductors. But there were problems. A catalyst in the process was leaving an unwanted metallic residue that degraded the chip. To avoid the residue, Hedrick, an advanced organic materials scientist, switched to organic catalysts. Then he had a conversation with Yiyan Yang, group leader at the Institute of Bioengineering and Nanotechnology in Singapore. “You should be using these in medicine,” she told Hedrick.
Hedrick did more than that. He helped set up a collaboration between IBM and the Institute.
“We make these polymer materials, and the group in Singapore does the biological testing,” says Engler, whose duties center on creating materials and interacting with the researchers at the Institute. “They provide us with the data and make suggestions on what I can do to make the materials better.”
In 2011, that alliance unveiled polymer nanostructures that detect and destroy infectious diseases and antibiotic-resistant bacteria like Methicillin-resistant Staphylococcus aureus (MRSA). MRSA is deadly. In 2005, it was behind some 95,000 serious infections and nearly 19,000 hospital deaths in the United States alone. So finding a counteragent is clearly an important advance.
Nanostructures attack bacteria in a way that makes it difficult for the bugs to protect themselves through adaptation as they do with conventional antibiotics. When the polymers are dissolved in water, they assemble into a new structure that is designed to break through the bacteria's cell membranes, releasing the inner contents and resulting in death. The physicality of the attack means bugs are less likely to develop resistance to the nanoparticles.
How the nanostructures find their targets is as important as their attack mode. Bacterial membranes have a negative surface charge, unlike healthy cells which have a neutral surface charge. The researchers manipulate the nanoparticles' charge attracting them to the microbes and ignoring healthy cells.
The nanostructures are biodegradable and after they've done their work they are excreted from the body, rather than remaining behind and accumulating in the organs. Because they're biodegradable, they can't enter the food chain, a risk with conventional antibiotics and other drugs.
Engler says the nano approach has promise well beyond combating MRSA. “Polymers could be engineered to carry drugs to specific points in the body. For example, we could deliver anti-cancer drugs directly to tumors or provide the ability to cross the blood/brain barrier to treat diseases that affect the brain, such as Alzheimer's disease,” she says.
Unfortunately, deadly bacteria thrive even outside of the body – on medical equipment, on surfaces in treatment rooms, on the skin of patients, visitors and caregivers. Currently those infestations are countered with harsh disinfectants such as bleach or alcohol. But these disinfectants are not suitable for all situations. To combat those bugs, the researchers at IBM and the Institute of Bioengineering and Nanotechnology developed an antimicrobial hydrogel early in 2013.
The gel eradicates drug-resistant bacteria on contact. Integral to its structure are polymers that self assemble when mixed with water and heated to body temperature. Under those conditions they swell into a gel that is easy to manipulate. The polymers' interaction create a “molecular zipper” effect, linking together much like the teeth on a clothing zipper. The gel is biodegradable, biocompatible and non-toxic.
“What's very exciting is the gel also disrupts biofilm,” says Engler. Biofilm is formed when microorganisms link together on a surface and embed themselves in a matrix of polymers they've excreted. Dental plaque is a biofilm, for example. “The biofilm matrix is hard to penetrate,” she says. “Tooth plaque needs to be manually scraped off.”
Engler says the gel has numerous potential uses. It could be used as a lubricous coating for catheters, greatly reducing a common source of infection. It also has potential for dentistry, she says. And surprisingly, for the cleaning of food machines. “The sugar and water in a soda machine make an ideal environment for bacteria. The hydrogel would eliminate the need to dismantle and clean the machine.”
So far the bacteria-killing nanomedicine has been applied only in laboratory conditions. It will need much more testing and commercial development before it can be used on humans. But IBM won't be doing that work. “We're a technology company, not a pharmaceutical firm,” says Engler. “We're looking for partners who will work with us to continue the development of these breakthroughs.”