Injected into mice suffering from a sepsis-related brain condition as part of a new study, microscopic bits of gold caused improvements by reducing inflammation and protecting some functions, in the latest demonstration of gold nanoparticles’ potential medical value.
In a paper published Feb. 19 in the Journal of Nanobiotechnology, Brazilian researchers said their promising results were the first to reduce brain inflammation with gold nanoparticles. They conducted the study on sepsis-associated encephalopathy, which currently has no approved treatments.
Gold has a long history of being employed as a medical tool and has been used as an antimicrobial agent since ancient times. For several decades, injections of the precious metal were also used to treat rheumatoid arthritis and other inflammatory conditions, before being replaced by more effective drugs. The mechanisms through which gold causes antimicrobial and anti-inflammatory effects are not fully understood, though some of it stems from its ability to “pop” cell walls and inhibit pro-inflammation compounds in cells.
Nanoparticle forms of gold and other precious metals are still popular subjects of medical research, pursued for applications ranging from diagnostic tools to drug delivery and cancer treatment.
Stephen Rodrigues, the study’s lead author and a professor of pharmacology at the University of São Paulo, said his journey with gold nanoparticles began with a 2014 investigation into their toxicity in blood vessels. He and his coauthors found they did not cause cell death — and, unexpectedly, demonstrated anti-inflammatory effects.
His latest research honed in on sepsis-associated encephalopathy, or the brain-related effects of sepsis that include lesions, comas and problems with neurotransmission. Sometimes known as “blood poisoning,” sepsis is caused by an imbalanced immune response to an infection that also attacks the body. It is often contracted in the hospital and is a leading killer in intensive care units.
The study used solutions of gold nanoparticles 20 nanometers wide — one-fortieth the width of a human hair — and injected them into the veins of mice either two or four hours after they were induced with sepsis-associated encephalopathy.
Compared with control mice with sepsis, the mice treated with gold had reduced white blood cells and other inflammatory markers in cerebral blood vessels. They were protected from failures in the blood-brain barrier, which restricts pathogens and many compounds from entering the brain.
“We saw a huge, good reduction in the flow in the inflammatory parameters in the brain,” Rodrigues said.
The team also found that the gold nanoparticles did not interfere with the improved survival rate caused by antibiotics, suggesting that the two treatments could be safely used in conjunction. The nanoparticles, however, did not improve survival rates.
The results were the same for injections given at both times, implying “a larger therapeutic window” for the treatment, the researchers wrote. They were compelling enough for the São Paulo professor to say that the treatment is ready for human testing for sepsis-associated encephalopathy.
“If any company is interested, I think this kind of treatment could already be tested in the clinical [trials],” Rodrigues said. “It is a possibility because there is no treatment for sepsis-associated encephalopathy yet.”
Gold-nanoparticle treatments show promise to be a “silver bullet,” he said, because they have been used to treat a range of diseases such as diabetes and asthma in animals.
Rodrigues said his lab plans to test the gold-nanoparticle treatment in other encephalopathy conditions. He and his colleagues had previously found that the treatment did not work on glioblastoma, the most aggressive form of brain cancer.
Rodrigues also noted that sepsis is a common cause of death among COVID-19 patients, so gold nanoparticles could be used to improve their cerebral septic conditions if the treatment is tested.
The study “Gold nanoparticles reduce inflammation in cerebral microvessels of mice with sepsis,” published Feb. 19 in the Journal of Nanobiotechnology, was authored by Davide Di Bella, João Ferreira, Renee de Nazare Silva, Cinthya Echem, Aline Milan, Eliana Akamine, Maria Carvalho and Stephen Rodrigues, University of São Paulo.