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WITH NANOPARTICLES AGAINST DANGEROUS BACTERIA

Multi-resistant pathogens are a serious and growing problem in modern medicine. Where antibiotics remain ineffective, these bacteria can cause life-threatening infections. Researchers at Empa and ETH Zurich have now developed novel nanoparticles that can be used to detect and kill multidrug-resistant pathogens hiding in body cells, as they write in a recent study in the journal Nanoscale.

In the "humanity versus bacteria" arms race, bacteria are currently ahead. Our former wonder weapons, antibiotics, are failing more and more frequently against germs that use tricky maneuvers to protect themselves from the effects of the drugs. Some species even retreat into the interior of human body cells, where they then remain unchallenged by the immune system. These particularly feared pathogens include so-called multi-resistant staphylococci (MRSA), which can cause life-threatening diseases such as blood poisoning or pneumonia.

In order to detect the germs in their hiding place and render them harmless, a team of researchers from Empa and ETH Zurich has now developed nanoparticles that use a completely different mechanism of action than conventional antibiotics: Whereas antibiotics have difficulty penetrating body cells, these nanoparticles, due to their small size and composition, manage to be smuggled into the interior of the affected cell. Once there, they fight the bacteria.

Bioglass and metal

To this end, the team led by Inge Herrmann and Tino Matter used the material cerium oxide, which in its nanoparticle form has antibacterial and anti-inflammatory effects. The researchers combined the nanoparticles with a bioactive ceramic material known as bioglass. Bioglass is interesting for medicine because it has versatile regenerative properties and is used, for example, for the reconstruction of bones and soft tissues.

Finally, nanoparticle hybrids of cerium oxide and bioglass were produced by flame synthesis. The particles have already been successfully used as wound adhesives, whereby several interesting properties can be exploited simultaneously: Thanks to the nanoparticles, bleeding can be stopped, inflammation dampened and wound healing accelerated. In addition, the novel particles show a significant effect against bacteria, while the treatment is well tolerated by human cells. Only recently, the new technology was successfully patented. The team has now published their results in the scientific journal "Nanoscale" in the "Emerging Investigator Collection 2021". Tino Matter is currently working on bringing the new technology to market. His startup anavo medical has already celebrated several successes - among others, it was among the three finalists of the Swiss Technology Awards.

Tricky germs

Among bacteria, there are some particularly tricky pathogens that penetrate body cells where they are invisible to the immune system. In this way, they survive periods when the body's defenses are on alert. This phenomenon is also known for staphylococci. They can retract into cells of the skin, connective tissue, bone and immune system. The mechanism of this persistence is not yet fully understood.

Staphylococci are mostly harmless germs that can occur on the skin and on mucous membranes. Under certain conditions, however, the bacteria flood the body and trigger severe inflammation, even toxic shock or blood poisoning. This makes staphylococci the leading cause of death from infections with just one type of pathogen.

Particularly precarious is the increasing number of staph infections that no longer respond to treatment with antibiotics. MRSA, multi-resistant germs, are particularly feared in hospitals, where they cause poorly treatable wound infections as nosocomial pathogens or colonize catheters and equipment. In total, around 75,000 hospital infections occur in Switzerland every year, 12,000 of which are fatal.

Destroy bacteria

The researchers were able to demonstrate the interactions between the hybrid nanoparticles, the somatic cells and the germs using electron microscopy studies, among other things. When infected cells were treated with the nanoparticles, the bacteria inside the cells began to dissolve. If, on the other hand, the uptake of the hybrid particles was specifically blocked by the researchers, the antibacterial effect also stopped.

The exact mechanism of action of the cerium-containing particles is not yet fully understood. It has been proven that other metals also exhibit antimicrobial effects. Cerium, however, is less toxic to body cells than silver, for example. The researchers currently assume that the nanoparticles act on the cell membrane of the bacteria, producing reactive oxygen compounds that lead to the destruction of the germs. Since the membrane of human cells has a different structure, body cells are spared this process.

Against such a mechanism, the researchers believe, fewer resistances would presumably be able to develop. "In addition, the cerium oxide particles regenerate again over time, so that the oxidative effect of the nanoparticles on the bacteria sets in again," says Empa researcher Tino Matter." In this way, the cerium particles could have a lasting effect.

Next, the researchers want to analyze the interactions of the particles in the infection process in more detail in order to further optimize the structure and composition of the nanoparticles. The goal is to develop a simple, robust antibacterial agent that is effective inside infected cells.

This article was originally posted by EMPA

 

 

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