Stop tooth decay before it starts, without killing bacteria

Oral bacteria are ready to act as soon as the dental hygienist finishes scraping the plaque from a patient’s teeth. Consuming sugar or other carbohydrates causes bacteria to quickly rebuild this hard, sticky biofilm and produce acids that corrode tooth enamel, leading to cavities. Scientists are now reporting a treatment that could one day stop the formation of plaque and cavities, using a new type of formulation of cerium nanoparticles that would be applied to teeth at the dentist.

The researchers will present their progress towards this goal today at the American Chemical Society (ACS) Fall 2020 Virtual Meeting and Expo.

The mouth contains more than 700 species of bacteria, explains Russell Pesavento, DDS, Ph.D., principal investigator of the project. They include beneficial bacteria that help digest food or control other germs. They also include harmful streptococcal species, especially Streptococcus mutans. Soon after cleaning, these bacteria stick to the teeth and start to multiply. With sugar as the energy source and building block, microbes gradually form a tough film that cannot be easily brushed off. As bacteria continue to metabolize sugar, they produce acidic byproducts that dissolve tooth enamel, paving the way for cavities.

Dentists and consumers can fight back with products that include stannous fluoride to inhibit dental plaque and silver nitrate or silver diamine fluoride to stop existing tooth decay. Researchers have also studied nanoparticles of zinc oxide, copper oxide or silver to treat dental infections. While such bactericidal agents have their place in dentistry, repeated applications could result in both stained teeth and bacterial resistance, according to Pesavento of the University of Illinois at Chicago. “Plus, these agents aren’t selective, so they kill many types of bacteria in your mouth, even the good ones,” he explains.

So Pesavento wanted to find an alternative that wouldn’t indiscriminately kill bacteria in the mouth and help prevent tooth decay, rather than treating cavities after the fact. He and his research group turned to cerium oxide nanoparticles. Other teams had examined the effects of various types of cerium oxide nanoparticles on microbes, although only a few looked at their effects on clinically relevant bacteria under the initial conditions of biofilm formation. Those who did have prepared their nanoparticles via redox reactions or pH-driven precipitation reactions, or purchased nanoparticles from commercial sources. These earlier formulations had no effect or even promoted biofilm growth in lab tests, he says.

But Pesavento persevered because the properties and behavior of nanoparticles depend, at least in part, on how they are prepared. His team produced their nanoparticles by dissolving ceric ammonium nitrate or sulfate salts in water. Other researchers had previously made the particles this way but had not tested their effects on biofilms. When the researchers seeded polystyrene plates with S. mutans in the growth media and fed the bacteria with sugar in the presence of the cerium oxide nanoparticle solution, they found that the formulation reduced biofilm growth by 40% compared to plaques without nanoparticles, although they did not are unable to dislodge existing biofilms. Under similar conditions, silver nitrate – a known anticavity agent used by dentists – showed no effect on biofilm growth.

“The advantage of our treatment is that it appears to be less harmful to oral bacteria, in many cases not killing them,” Pesavento says. Instead, the nanoparticles simply stopped microbes from sticking to polystyrene surfaces and forming clinging biofilms. In addition, the toxicity and metabolic effects of nanoparticles in human oral petri dish cells were lower than that of silver nitrate.

Pesavento, which obtained a patent in July, would like to combine the nanoparticles with enamel-strengthening fluoride in a formulation that dentists could paint on a patient’s teeth. But, he notes, a lot of work needs to be done before this concept can be realized. For now, the team is experimenting with coatings to stabilize the nanoparticles at a neutral or slightly basic pH – closer to the pH of saliva and healthier for the teeth than the current acidic solution. His team also began working with bacteria linked to the development of gingivitis and found a particular coated nanoparticle that outperformed stannous fluoride by limiting the formation of adherent biofilms under similar conditions. Pesavento and his team will continue to test the treatment in the presence of other bacterial strains commonly found in the mouth, as well as to test its effects on human cells in the lower digestive tract to gain a better sense of overall patient safety.