Combined treatment takes a bite out of tooth decay

Getting a toothache or discovering a cavity is a universal dread. Dental caries, more commonly known as tooth decay, is an insidious adversary, taking a toll on millions of mouths worldwide. Tooth decay can lead to pain, tooth loss, infection and, in severe cases, even death.

While fluoride-based treatments have long been the gold standard in dentistry, this single approach is now outdated and of limited effect. Current treatments do not sufficiently control biofilm – the main culprit behind dental caries – and at the same time prevent enamel demineralization. This dual dilemma becomes particularly pronounced in high-risk populations where disease onset can be rapid and severe.

Now, a study by a team of researchers led by Hyun (Michel) Koo of the University of Pennsylvania School of Dental Medicine in collaboration with David Cormode of Penn’s Perelman School of Medicine and School of Engineering and Applied Sciences has discovered an unexpected synergy in the fight against dental caries. Their research found that the combination of ferumoxytol (Fe) and stannous fluoride (SnF₂) may indicate a powerful solution against dental caries. Their findings were published in Nature Communications.

“Traditional treatments often fall short in managing the complex biofilm environment in the mouth,” says Koo, co-senior author on the study. “Our combination treatment not only increases the effectiveness of each agent, but does so at a lower dose, hinting at a potentially revolutionary method for preventing caries in high-risk individuals.”

Their findings include the ability of Fer to stabilize SnF₂increased catalytic activity of Fer when combined with SnF₂, and the formation of a Fe/Sn/F-rich protective film on tooth enamel, which may serve as a shield against further demineralization. Furthermore, this combined therapy does not disrupt the ecological balance of the oral microbiota and has no negative side effects on the surrounding host tissues.

Cormode, co-senior author of the paper, says: “What excites us most about these findings is the multifaceted approach to caries prevention. It’s not just about inhibiting bacterial growth or protecting enamel; is a holistic method that targets both biological and physicochemical aspects of dental caries.”

The researchers also note that, beyond this protective and proactive measure, an intriguing secondary benefit emerged. Many children with severe tooth decay also suffer from iron deficiency anemia. The use of Fer can treat dental problems and anemia simultaneously.

Reflecting on the next steps, Koo says, “While we are pleased with these initial findings, we still intend to dig deeper into understanding the intricate mechanisms of Fer and SnF₂ synergize to enhance therapeutic effects.”

Another important advantage of this combined treatment is the promise of a rapid transition to clinical applications. Since Fer is a nano-particle formulation of iron oxide, using it topically at a fraction of its approved systemic dose could speed its way to practical applications and commercialization without the long and arduous journey of new approvals of drugs.

Looking ahead, further research is required into the exact mechanisms of the interaction between SnF2 and Fer, the generation process of reactive oxygen species, and the formation and efficacy of the protective enamel film.

“There is potential here not only in dental care, but in exploring how this combination can be targeted against other biofilms,” says Cormode.

Hyun (Michel) Koo is a professor in the Department of Orthodontics and the Divisions of Pediatric Dentistry and Community Oral Health and co-founder of the Center for Innovation and Precision Dentistry at the University of Pennsylvania School of Dental Medicine.

David Cormode is an associate professor of radiology and bioengineering with appointments at Penn’s Perelman School of Medicine and School of Engineering and Applied Sciences.

Other authors are Yue Huang, Nil Kanatha Pandey, Shrey Shah and Jessica C. Hsu of Penn’s Perelman School of Medicine; Yuan Liu, Aurea Simon-Soro, Zhi Ren, Zhenting Xiaang, Dongyeop Kim, Tatsuro Ito, Min Jun Oh, and Yong Li from Penn’s School of Dental Medicine; Paul. J Smeets, Sarah Boyer, Xingchen Zhao and Derk Joester from Northwestern University; and Domenick T. Zero of Indiana University.

The work was supported by the National Institutes of Health (grants R01-DE025848 and TL1TR001423 and awards S10OD026871 and R90DE031532) and the National Science Foundation (awards ECCS-2025633 and DMR-1720139).