Nanoparticles are a relatively new competitor in the fight against antibiotic-resistant bacteria. A team of researchers from Swiss Federal Laboratories for Materials Science and Technology (Empa) and ETH Zurich is developing nanoparticles that use a completely different mode of action from conventional antibiotics. While antibiotics have difficulty in penetrating human cells, nanoparticles, due to their small size and structure, can penetrate the membrane of affected cells. Because of that, they play a role in combatting intracellular pathogens, like multi-resistant staphylococci (MRSA).

Their latest work is published in the journal, Nanoscale, in the article, “Inorganic nanohybrids combat antibiotic-resistant bacteria hiding within human macrophages.”

The team used cerium oxide, a material that has antibacterial and anti-inflammatory properties in its nanoparticle form. The researchers combined the nanoparticles with a bioactive ceramic material known as bioglass. Bioglass is of interest in the medical field because it has versatile regenerative properties and is used, for example, for the reconstruction of bones and soft tissues.

They then synthesized flame-made nanoparticle hybrids made of cerium oxide and bioglass. The particles have already been successfully used as wound adhesives. Thanks to the nanoparticles, bleeding can be stopped, inflammation can be dampened, and wound healing can be accelerated. In addition, the novel particles showed significant effectiveness against bacteria, while the treatment is well tolerated by human cells.

In this work, the authors wrote, load and carrier are combined into one functional inorganic nanoparticle system, which unites antimicrobial activity with mammalian cell compatibility. They noted: “This work presents the first demonstration of antibacterial activity of ceria-based nanoparticles inside of mammalian cells and offers a route to straightforward and robust intracellular antibacterial agents that do not depend on payload delivery or biological constituents.”

The researchers were able to show interactions between the hybrid nanoparticles, the human cells, and the bacteria using electron microscopy, among other methods. If infected cells were treated with the nanoparticles, the bacteria inside the cells began to dissolve. However, if the researchers specifically blocked the uptake of the hybrid particles, the antibacterial effect was gone.

The particles’ exact mode of action is not yet fully understood. It has been shown that other metals also have antimicrobial effects. However, cerium is less toxic to human cells than, for instance, silver. Scientists currently think that the nanoparticles affect the cell membrane of the bacteria, creating reactive oxygen species that lead to the destruction of the bacteria. Since the membrane of human cells is structurally different, our cells are not affected by this process.

The researchers think that resistance is less likely to develop against a mechanism of this kind. “What’s more, the cerium particles regenerate over time, so that the oxidative effect of the nanoparticles on the bacteria can start all over again,” said Tino Matter, PhD, a post-doc at ETH Zurich, and first author on the paper. In this way, the cerium particles could have a long-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.