Researchers from the University of California at San Diego created macrophage nanosponges that are wrapped in the cell membranes of macrophages and can safely absorb and remove sepsis-causing molecules from the bloodstream. So far, the nanosponges have improved survival rates in mice with sepsis.
Sepsis occurs when immune chemicals that are released in the body to fight infection end up causing widespread inflammation, blood clots and leaky vessels, according to the National Institute of General Medical Sciences. Approximately 1 million Americans develop sepsis per year and about 28-50% of people who develop sepsis die. It also accounts for the most hospital readmissions per year than the four medical conditions that are tracked by the U.S. government (heart attacks, heart failure, COPD and pneumonia).
Typical treatment of sepsis usually involves administering antibiotics that can eliminate sepsis-causing bacteria, but can’t limit inflammation.
Some bacteria that causes sepsis secrete toxic molecules known as endotoxins. Endotoxins are recognized as dangerous by macrophages, which are white blood cells that play a role in inflammation. When the macrophages detect endotoxins, they produce inflammation-causing proteins called pro-inflammatory cytokines that make other macrophages produce more cytokines.
“To effectively manage sepsis, you need to manage this cytokine storm,” Liangfang Zhang, professor of nano engineering at UC San Diego and researcher, said in a press release.
The researchers showed that macrophage nanosponges could neutralize both endotoxins and pro-inflammatory cytokines in the bloodstream because they naturally bind to macrophage cell membranes.
The nanosponges act as universal traps for different sepsis-causing molecules. Since the sponges are covered in macrophage cell membrane, they are able to appear as the body’s own immune cells and run its course through the body without causing an immune system response.
“They can work across different bacterial genus, species and strains,” Zhang said.
Zhang and the researchers on this project used macrophage cells from mice to create nanosponges. The cells were soaked in a solution to make the cells burst and leave the membranes behind. Using a centrifuge, the researchers collected the membranes and mixed them with ball-shaped nanoparticles made of a biodegradable polymer. The mixing allowed for the nanoparticles to be coated in macrophage cell membranes.
The researchers gave the macrophage nanosponges to mice that had a lethal dose of E. coli. Four out of 10 of the mice were kept alive. Mice that were left untreated died. The research also showed that with just one dose of the macrophage nanosponges, the levels of endotoxins and pro-inflammatory cytokines were significantly reduced in the mice that were treated.
Zhang is currently working with biopharmaceutical companies to bring the macrophage nanosponges to clinical use and hopes to include manufacturing the nanosponges in large scales while testing them in large animal trials.
The research was published in the journal Proceedings of the National Academy of Sciences and was supported by the National Science Foundation, the Defense Threat Reduction Agency Joint Science and Technology Office for Chemical and Biological Defense and the National Institutes of Health.
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