Biting a toothache or discovering a cavity is a universal dread. Dental caries, more commonly known as tooth decay, is an insidious adversary, affecting millions of mouths around the world. 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While fluoride-based treatments have long been the gold standard in dentistry, this unique approach is now outdated and of limited effect. Current treatments do not adequately control biofilm – the main culprit behind tooth decay – and at the same time prevent enamel demineralization. This dual dilemma becomes particularly acute in high-risk populations where disease onset can be both rapid and severe.
Now, a study by a team of researchers led by Hyun (Michel) Koo from University of Pennsylvania‘small School of Dentistry in cooperation with David Cormond of Pence Perelman School of Medicine and Faculty of Engineering and Applied Sciences has revealed an unexpected synergy in the fight against tooth decay. Their research revealed that the combination of ferumoxytol (Fer) and stannous fluoride (SnF2) could show a strong anti-caries solution. Their findings were published in Nature communications.
“Traditional treatments often fail to manage the complex biofilm environment in the mouth,” says Koo, senior co-author of the study. “Our combined treatment not only enhances the effectiveness of each agent, but does so at a lower dose, implying a potentially revolutionary method for preventing caries in high-risk individuals.”
Their findings include the ability of Fer to stabilize SnF2the increased catalytic activity of Fer when combined with SnF2and the formation of a protective Fe/Sn/F-rich film on tooth enamel, which may serve as a shield against further decalcification. Furthermore, this combined treatment does not disturb the ecological balance of the oral microflora and has no negative side effects on the surrounding host tissues.
Cormode, senior co-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 the biological and physicochemical aspects of dental caries.”
The researchers also note that, beyond this protective and preventive measure, an interesting secondary benefit emerged. Many children with severe caries also suffer from iron deficiency anaemia. Using Fer can treat dental concerns and anemia at the same time.
Reflecting on the next steps, Koo says, “While we are pleased with these initial findings, we still aim to dig deeper into understanding the complex modes of Fer and SnF2 they work together to enhance therapeutic effects.”
Another major advantage of this combination therapy is the promise of a rapid transition to clinical applications. Since Fer is an iron oxide nanoparticle formulation, its topical use at a fraction of its approved systemic dose could accelerate its path to practical applications and commercialization without the long, arduous journey of new drug approvals.
Looking to the future, further research is needed on the exact interaction mechanisms between SnF2 and Fer, the process of producing reactive oxygen species, and the formation and effectiveness of the protective enamel film.
“There is potential here not only in dental care but also in exploring how this combination can target other biofilms,” says Cormode.
Hyun (Michel) Koo is a professor at Department of Orthodontics and in the departments of Pediatric Dentistry and Community Oral Health and the co-founder of the Center for Innovation & Precision Dentistry at the University of Pennsylvania School of Dentistry.
David Cormode is an associate professor of radiology and bioengineering with appointments in Penn’s Perelman School of Medicine and School of Engineering and Applied Science.
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 of Penn’s School of Dental Medicine. Paul. J Smeets, Sarah Boyer, Xingchen Zhao and Derk Joester of 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).
