A Nanoscale Solution To Sepsis

Potent antioxidant nanoparticles that can mop up excess reactive oxygen species could help prevent sepsis-related deaths.

AsianScientist (July 19, 2017) – Scientists in Korea have created antioxidant nanoparticles that could prevent sepsis from becoming life-threatnening. Their findings are reported in the journal Angewandte Chemie.

Sepsis is a condition that arises when the body’s response to an infection causes damage to tissues and organs. During sepsis, cells are swamped with reactive oxygen species generated in an abnormal response by the immune system. By interfering with this fatal inflammatory pathway, new treatment schemes could be developed that prevent sepsis-related deaths.

In this study, the researchers found that nanoparticles made of zirconium oxide (zirconia) and cerium oxide (ceria) act as effective scavengers of oxygen radicals. The nanoparticles greatly enhanced the survival rate in animal models of sepsis.

A team led by Professor Heyon Taeghwan from Seoul National University and Dr. Lee Seung-Hoon at Seoul National University Hospital showed that ceria nanoparticles can quickly convert between two oxidation states—Ce(3+) and Ce(4+)—to quench typical oxygen radical species like the superoxide anion, the hydroxyl radical anion or hydrogen peroxide.

However, for these nanoparticles to function effectively in living cells, they must be small and able to pass through the cell membrane. Moreover, the cerium ion responsible for the quenching effect, Ce(3+), should be accessible on the surface of the nanoparticles and it must be regenerated after reacting with free radicals.

To meet all these criteria, the scientists discovered that it was critical to add zirconium ions to the structure of the nanoparticles.

“The Zr(4+) ions control the Ce(3+)-to-Ce(4+) ratio as well as the rate of conversion between the two oxidation states,” said the researchers.

The researchers then tested the nanoparticles for their ability to detoxify reactive oxygen species. In live animal models, the nanoparticles accumulated in organs where severe immune responses occurred and successfully quenched the reactive oxygen species at the inflamed site. Importantly, the treated mice and rats had a far higher survival rate.

“A single dose of ceria-zirconia nanoparticles successfully attenuated the vicious cycle of inflammatory responses in two sepsis models,” the researchers added.

This work demonstrates an alternative to treating sepsis that does not depend on killing the bacteria using antibiotics. As resistance against antibiotics is growing, scientists can turn to the inflammatory pathway as a target for new treatment strategies.

The article can be found at: Soh et al. (2017) Ceria–Zirconia Nanoparticles as an Enhanced Multi-Antioxidant for Sepsis Treatment.


Source: Wiley; Photo: Shutterstock.
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