Researchers at IBM are designing nanoparticles that kill bacteria by poking holes in them. The scientists hope that the microbes are less likely to develop resistance to this type of drug, which means it could be used to combat the emerging problem of antibiotic resistance. This type of drug has not had much success in clinical trials in the past, but initial tests of the nanoparticles in animals are promising.
Drug-resistant bacteria have become a major problem. In 2005, nearly 95,000 people in the United States developed a life-threatening staph infection resistant to multiple antibiotics, according to the U.S. Centers for Disease Control and Prevention. It takes just one to two decades for microbes to develop resistance to traditional antibiotics that target a particular metabolic pathway inside the cell, says Mary B. Chan-Park, professor of chemical and biological engineering at Nanyang Technological University in Singapore, who was not involved with the research. In contrast, drugs that compromise microbes’ cell membranes are believed to be less likely, or slower, to evoke resistance, she says.
“We’re trying to generate polymers that interact with microbes in a very different way than traditional antibiotics,” says James Hedrick, a materials scientist at IBM’s Almaden Lab in San Jose, California. To do this, Hedrick’s research group took advantage of past work on a library of polymer building blocks that can be mixed and matched to make complex nanoparticles. To make a nanoparticle that would selectively attack bacterial membranes and then break down harmlessly inside the body, the IBM group put together three types of building blocks. At the center of the polymer sequence is a backbone element that’s water-soluble and tailored to interact with bacterial membranes. At either end of the backbone is a hydrophobic sequence. When a small amount of these polymer chains are added to water, the differences between the ends and the middle of the sequence drive the polymers to self-assemble into spherical nanoparticles whose shell is entirely made up of the part that will interact with bacterial cells. This work is described this week in the journal Nature Chemistry.
IBM’s labs aren’t equipped for biological tests, so the researchers collaborated with Yi Yan Yang at the Singapore Institute of Bioengineering and Nanotechnology to test the nanoparticles. They found that the nanoparticles could burst open and kill gram-positive bacteria, a large class of microbes that includes drug-resistant staph. The nanoparticles also killed fungi. Other types of deadly bacteria that have different types of cell membranes would not be vulnerable to these nanoparticles, but the IBM researchers say they are developing nanoparticles that can target these bacteria, too, though it is more difficult. “Through molecular tailoring,” says Robert Allen, senior manager of materials chemistry at IBM Almaden, “we can do all sorts of things”—designing particles with a particular shape, charge, water solubility, or other property.