Nanoparticle-Based Treatment for Sepsis Tested in Mice to Help Prevent Multiorgan Injury

In a new study, the lab of Shaoqin "Sara" Gong, a professor at the Wisconsin Institute for Discovery at the University of Wisconsin - Madison, reported a new nanoparticle-based treatment that delivers anti-inflammatory molecules and antibiotics.

A Phys.org report said that the new system saved the lives of mice with an induced version of sepsis intended to function as a model for infections in humans, and is promising "proof-of-concept" for a possible new treatment, pending additional studies.

Essentially, sepsis, the body's overreaction to an infection, affects more than 1.5 million people and claims the lives of at least 270,000 people each year in the United States alone.

The standard treatment of fluids and antibiotics is ineffective in many patients, as well as those who survive a higher death risk.

New Nanoparticles

In this new study published in Nature Nanotechnology, the researchers reported that the new nanoparticles delivered the chemical NAD+ or its reduced form NAD(H), a molecule that has an important role in the biological processes that produce energy, preserve genetic material, and help cells adjust to, and overcome stress.

Whereas NAD(H) is well known for its anti-inflammatory function, its clinical application has been impeded because NAD(H) cannot be directly taken up by cells.

Gong explained that to enable clinical translation, they need to find a way to deliver NAD(H) to the targeted cells or organs. To achieve this objective, the researchers developed a couple of nanoparticles that can transport and release NAD(H) directly into the cell while averting premature drug release and degradation in the bloodstream.

Gong holds appointments in the Department of Biomedical Engineering and the UW School of Medicine and Public Health's Department of Ophthalmology and Visual Sciences.

Sepsis, a Possibly Fatal Disease

This interdisciplinary work was led by Gong, together with Mingzhou Ye and Yi Zhao, two postdoctoral fellows in the Gong lab. Professor John-Demian Sauer from the Department of Medical Microbiology and Immunology also collaborated on this project.

Essentially, sepsis can be fatal in two phases. First, an infection starts in the body. The immune system then responds by developing drastic inflammation that damages blood flow and forms blood clots, leading to tissue death and stimulating a chain reaction resulting in organ failure.

Thereafter, the body overcorrects itself by repressing the immune system, increasing infection vulnerability. Controlling complications caused by inflammation is essential in sepsis treatment.

The lipid-coated calcium phosphate or metal-organic framework nanoparticles designed by the Gong lab can be used to co-deliver NAD(H) and antibiotics.

Nanoparticle Treatment in Mice

Gong's lab examined the NAD(H)-loaded nanoparticles in several mouse models, including endotoxemia, multidrug-resistant pathogen-induced polymicrobial bacteremia, and puncture-induced sepsis model with secondary infection by a common illness-causing bacteria identified as P. aeruginosa.

The nanoparticle treatment did much better than NAD(H) alone, as stated in the University of Wisconsin-Madison report. For example, in an endotoxemia mouse model, mice that didn't have any treatment or were treated with free NAD(H) died within two days.

On the contrary, mice treated with nanoparticles loaded with NAD(H) survived. These animal studies showed that the NAD(H) nanoparticles could help keep a healthy immune system, support the function of the blood vessel, and prevent multiorgan injury.

Gong described their findings and said the NAD(H) nanoparticles could potentially treat many other illnesses because NAD(H) involves many biological pathways. He added that there is strong evidence for using NAD(H) "as an intervention or aid in critical illnesses."

Related information about nanoparticles that can treat sepsis is shown on Arirang News's YouTube video below:

Check out more news and information on Nanoparticles in Science Times.