Sepsis, the body’s overreaction to infection, affects more than 1.5 million people and kills at least 270,000 people a year in the United States alone. Antibiotic and fluid therapy are often ineffective for many patients, and survivors have a higher risk of death. In a new study (The new nanoparticles help treat sepsis in mice) published in the journal Nature Nanotechnology today, the laboratory of Shaoqin “Sarah” Gong, a professor at the Wisconsin Institute for Discoveries at the University of Wisconsin-Madison, reports a new nanoparticle-based treatment that is an anti-inflammatory molecule. administered an antibiotic.
The new system (The new nanoparticles help treat sepsis in mice) saves the lives of mice with an induced version of sepsis to serve as a model of human infections and is good evidence of a concept for a potential new therapy that is awaiting further investigation.
The new nanoparticles supply the chemical NAD + or its reduced form NAD (H), a molecule that plays an important role in biological processes that produce energy, save genetic material and help cells adapt and overcome stress. While NAD (H) is known for its anti-inflammatory function, it prevents clinical application because NAD (H) is not directly absorbed by cells.
“To be able to clinically translate, we need to find a way to efficiently deliver NAD (H) to target organs or cells. To achieve this, we have designed several nanoparticles that can transport and release NAD (H) directly into cells, while preventing premature drug release and blood flow damage, ”said Gong, who also has meetings with the Institute of Biomedical Engineering and the Institute of Ophthalmology and Visual Sciences UW School of Medicine and Public Health.
The interdisciplinary work was conducted by Gong with Mingzhou Ye and Yi Zhao, two postdoctoral fellows in Gong’s laboratory. John-Demian Sauer, a professor at the Institute of Medical Microbiology and Immunology, also collaborated on the project. Sepsis can be fatal in two stages. First, the infection begins in the body. The immune system responds by producing severe inflammation that affects the bloodstream and forms blood clots that can cause tissue death and trigger chain reactions that lead to organ failure. Subsequently, the body corrects by suppressing the immune system, which in turn increases the susceptibility to infection. Prevention of complications caused by inflammation is essential in the treatment of sepsis. Lipid-coated calcium phosphate as a metal-organic nanoparticle structure designed by Gong can be used to supply NAD (H) and antibiotics. Gong’s laboratory tested NAD (H) -charged nanoparticles in several mouse models, including endotoxemia, polymicrobial bacteremia caused by multidrug-resistant pathogens, and a puncture-induced sepsis model with secondary infection of common bacteria causing a disease called P. aeruginosa.
Nanoparticle treatment was more effective than using NAD (H) alone. For example, in an endotoxemic mouse model, mice died untreated or were treated with free NAD (H) within two days. In contrast, mice treated with NAD(H)-loaded nanoparticles all survived. These animal studies demonstrated that the NAD(H) nanoparticles can help maintain a healthy immune system, support blood vessel function and prevent multiorgan injury.
This technology may pave the road for the development of a new clinical therapy for sepsis that could also be applied in other inflammation-related scenarios, such as COVID-19 treatment. An additional benefit of this therapy is the ability to treat infection with lower amounts of antibiotics, which reduces their overuse. Further research in larger animal models will be necessary before clinical trials in people could begin. “NAD (H) nanoparticles have the potential to cure many other diseases because NAD (H) is involved in many biological pathways. There is strong evidence for the use of NAD (H) as an intervention or aid in critical diseases,” Gong said.
