Stop tooth decay before it starts – without killing bacteria

Oral bacteria are ready to jump into action the moment a dental hygienist removes the plaque from a patient’s teeth. Eating sugar like other carbohydrates ensures that the bacteria quickly build up this tough and sticky biofilm and produce acids that corrode tan enamel, leading to cavities. Scientists are now reporting a treatment that could prevent the formation of cavities and holes in the first place, with a new type of cerium nanoparticle formulation that would be applied to teeth at the dentist’s office.

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

The mouth contains more than 700 species of bacteria, says Russell Pesavento, DDS, Ph.D., the project’s lead researcher. They contain beneficial bacteria that help feed or keep other microbes in check. They also include harmful streptococcal species, including Streptococcus mutans. Soon after cleaning, these bacteria cling to teeth and begin to multiply. With sugar as an energy source and building blocks, the microbes gradually form a solid film that cannot be easily removed by brushing. While the bacteria continue to metabolize sugar, they make acidic by-products that dissolve tosamail, and pave the way for cavities.

Dentists and consumers can fight back with products including stannous fluoride to inhibit plaque, and silver nitrate or silver diamine fluoride to stop existing teeth. Researchers have also studied nanoparticles made of zinc oxide, copper oxide or silver to treat toxin infections. Although bactericidal agents like these have their place in dentistry, repeated applications can lead to both tooth decay and bacterial control, according to Pesavento, who is at the University of Illinois at Chicago. “Also, these agents are not selective in that they kill many types of bacteria in your mouth, even good ones,” he explains.

That said, Pesavento wanted to find an alternative that would not kill bacteria in the mouth involuntarily and that would help prevent tooth decay, instead of treating cavity after the fact. He and his research team turned to nano-particles of cerium oxide. Other teams had investigated the effects of different types of cerium oxide nanoparticles on microbes, although only a few had looked at their effects on clinically relevant bacteria under initial conditions for biofilm formation. Those who did so prepared their nanoparticles through oxidation company reactions or pH-driven precipitation reactions, or purchased nanoparticles from commercial sources. Those prior formulations had no effect or even promoted biofilm growth in lab tests, he says.

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

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

Pesavento, which obtained a patent in July, wants to combine the nanoparticles with enamel-enhancing 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 that concept can be realized. For now, the team is experimenting with coatings to stabilize the nanoparticles at a neutral or slightly alkaline pH – closer to the pH of saliva and healthier for teeth than the current acid solution. His team has also begun working with bacteria linked to the development of gingivitis and has found one particular coated nanoparticle that starves stannous fluoride while limiting the formation of adherent biofilms under similar conditions. Pesavento and his team will continue the treatment with tests in the presence of other bacterial strains that are typically present in the mouth, as well as the effects of their tests on human cells of the lower digestive tract to get a better feeling for general safety for patients.