Nanoparticle-based Treatment Show Promise in Mouse Models of Sepsis

Nanoparticle-based Treatment Show Promise in Mouse Models of Sepsis

Researchers have developed a new method for treating sepsis that has had promising results in studies on mice. Sepsis is caused when the body’s immune system goes into overdrive in response to an infection and starts attacking the body’s own organs and tissues. Sepsis is a life-threatening condition that requires emergency medical treatment, which can progress to septic shock, resulting in severe damage to organs or death.

According to data from the Centers for Disease Control and Prevention (CDC), at least 1.7 million people develop sepsis each year, resulting in 270,000 deaths. The treatment for sepsis is antibiotics, which can be effective if provided quickly, but some patients do not respond to treatment. Patients that survive sepsis can suffer long-term effects that can be extremely debilitating, and they face an increased risk of death.

A team of researchers led by Shaoqin Sarah Gong, professor at the Wisconsin Institute for Discovery at the University of Wisconsin–Madison, has been working on a new treatment for sepsis that involves nanoparticles, which deliver antibiotics and anti-inflammatory molecules. The new treatment was used in a study on mice with induced sepsis and improved the survival rate compared to the control group.

Sepsis involves major inflammation which can impair blood flow and leads to the formation of blood clots, which can cause organ death. In response, the body suppresses the immune system, which can lead to infections. Nicotinamide adenine dinucleotide (NAD+) is a molecule naturally produced in the body that has anti-inflammatory properties. There is potential for NAD+ to be used for the treatment of sepsis to reduce inflammation, however, NAD+ cannot be taken into cells directly, which has limited clinical applications.

The researchers loaded nanoparticles with a reduced form of NAD+ – NAD(H) – then engineered the NAD(H)-loaded nanoparticles to enable direct cellular transport to allow the delivery of NAD(H) to the targeted organs or cells along with antibiotics. The NAD(H)-loaded nanoparticles were engineered to prevent premature release of NAD(H) and degradation in the bloodstream.

The researchers tested their new treatment on several mouse models of sepsis, including endotoxemia, multidrug-resistant pathogen-induced polymicrobial bacteremia, and puncture-induced sepsis with secondary infection by P. aeruginosa. In the endotoxemia model, mice that received no treatment or were treated with NAD(H) alone died within two days, but all mice treated with the nanoparticles survived. The treatment was also effective in mice with multidrug-resistant pathogen-induced bacteremia, and improved outcomes for mice with secondary P. aeruginosa infections following caecal ligation and puncture.

“The NAD(H) nanoparticles have the potential to treat many other diseases because NAD(H) is involved with so many biological pathways. There is strong evidence for the use of NAD(H) as an intervention or aid in critical illnesses,” said Gong.

You can read more about the study in the paper – NAD(H)-loaded nanoparticles for efficient sepsis therapy via modulating immune and vascular homeostasis – which was recently published in Nature Nanotechnology. DOI: 10.1038/s41565-022-01137-w