Rather than targeting the bacteria, dentists at Semmelweis University, Hungary bank on the body’s immune response to combat the cells responsible for maintaining oral inflammation. This novel approach has been used in cancer therapy but has never been described in periodontology. Their aim is to create a dental hygiene product, such as a mouthwash, to supplement traditional methods.

Affecting 20-50% of the population worldwide, periodontitis, also called gum disease, is an infection that damages the soft and hard tissue around the teeth. If left untreated, it can destroy the bone and can lead to the loss of the tooth. To supplement regular treatments such as removal of the dental plaque or surgery, dentists at Semmelweis University looked for novel ways to combat this condition.

Rather than targeting the bacteria causing the inflammation, we used the body’s own immune cells to manage it,

says dr. Zoltán Géczi, assistant professor at Semmelweis University, Department of Prosthodontics and first author of the study describing the new approach. The Semmelweis researchers targeted macrophages, a type of white blood cells that have an integral part in the immune system with the role of eliminating foreign antigens, such as bacteria. One group, M1 macrophages, are associated with proinflammatory activation and mediate host defense against viruses and bacteria. The other, known as M2 macrophages, have anti-inflammatory and pro-healing functions. “One of our goals was to inactivate M1 macrophages and help them convert into M2 macrophages”, Géczi explains.

To do that, they created a complex with two components: silver, responsible for the antimicrobial effect and folic acid, that helps get that substance into the inflamed cell.

Folic acid (FA) is a nonimmunogenic, stable and cost-effective ligand with a high affinity for the cell surface folate receptors (FRs). FRs tend to increase drastically on the surface of the cells in inflamed environment thus helping locate the inflammation and distinguish between healthy and inflamed cells.

Silver, responsible for eliminating and transforming M1 macrophages, gets into the cell linked to FA. This is necessary because the very barriers that protect organs, cells, etc. from harmful substances also prevent active agents needed to fight pathogens or inflammation from entering. This approach is also called the Trojan-horse mechanism as the active ingredient gets into the cell camouflaged. 

The Trojan-horse mechanism has never been described in the field of periodontology before.

The phrase “Trojan horse” refers to a range of tactics used in drug research to deliver medications to the target in disguise, safely and effectively. The aim is to outsmart and penetrate barriers, such as the blood-brain barrier or the cell membrane. It is also used to specifically target the disease rather than the entire body, which also helps avoid undesired side effects.

Another condition of cell entry is size. The researchers used nanoparticle silver and folic acid as anything larger would be unable to pass through those barriers. Once inside the cell, the FA-silver complex breaks down, and the silver ion destroys the macrophages that maintain the inflammation.

Laboratory trials are ongoing; when the product is ready – in the form of mouthwash or gel – it will be applied locally in the oral cavity directly to the inflamed areas,

says dr. Zoltán Géczi.

Periodontal disease is an inflammation of the gums and the tissues that support the teeth caused by poor oral hygiene. When the teeth are not cleaned properly, food gets trapped in the spaces in between and a layer of film builds up  Over time this plaque hardens and if not removed, irritates the surrounding gum tissue. In its early stages, the process is reversible; removing the tartar can stop the inflammation. If the irritation persists, it can cause the gums and the bone to recede. In more severe cases, the tooth must be removed. This, however, can take years or even decades.

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