Researchers at Ohio State University have developed a novel nanotech approach to combating late-stage sepsis. Yizhou Dong, the study’s senior author, is an associate professor of pharmaceutics and pharmacology at Ohio State. He and his colleagues have developed a way to bolster a struggling immune system to empower it to fight against sepsis.
In their study, published in Nature Nanotechnology, the researchers took white blood cells from healthy mice, specifically monocytes from their bone marrow, and transformed them into macrophages, or immune system cells responsible for killing bacteria. Patients with sepsis typically have fewer macrophages and other immune cells in their body, and these cells are not as effective as they should be.
The researchers then further engineered the macrophages into a drug with further enhanced power to kill bacteria by adding a compound of acids, a vitamin, and a protein. These MACs (macrophages containing antimicrobial peptides linked to cathepsin B in the lysosomes) are “constructed by transfection of vitamin C lipid nanoparticles that deliver antimicrobial peptide and cathepsin B (AMP-CatB) mRNA.”
The research combined two prominent types of technology: using vitamins as the main component in making lipid nanoparticles and using those nanoparticles to capitalize on natural cell processes in the creation of a new antibacterial drug. According to Dong, “Macrophages have antibacterial activity naturally. So if we add the additional antibacterial peptide into the cell, those antibacterial peptides can further enhance the antibacterial activity and help the whole macrophage clear bacteria”.
In experiments where the MACs were administered to immunosuppressed mice with multidrug-resistant bacteria-induced sepsis, the MACs eliminated the bacteria in blood and major organs and dramatically improved survival rates. All bacteria were eliminated within two treatments, with each treatment consisting of about 4 million engineered macrophages. Dong believes “this cell therapy can help patients who get to the late stage of sepsis” when the immune system is compromised and ineffective at dealing with hostile bacteria, and “could be used in combination with current intensive-care treatment for sepsis patients.”
With the results published, Dong and colleagues will now aim for a human clinical trial within the next few years. “We hope to move the project to a clinical trial as soon as possible, but there is still a long way to go, I think,” Dong said. “In the future, if we overcome those challenges, we hope we can develop some sort of off-the-shelf therapy for late-stage sepsis.”