Trapping Toxins to Prevent Sepsis – Asian Scientist Magazine

AsianScientist (Jun. 14, 2023) – Researchers in Singapore have created multifunctional synthetic peptide nanonets as targeted therapies for sepsis. These nanonets help reduce inflammation caused by bacterial infections by catching both bacterial endotoxins and pro-inflammatory cytokines. The study was published in Advanced Healthcare Materials.

Sepsis is a life-threatening condition characterised by body’s extreme response to an infection. It happens when an already existing infection triggers a chain reaction throughout the body, most often in lungs, skin and gastrointestinal tract. Previously researchers have tried to develop targeted therapies against sepsis, but they have been largely unsuccessful.

The researchers of this study focused on multi-cytokine techniques to come up with a new method of treating sepsis. Previously the team had prepared a design of antimicrobial peptides that self-assemble into nanonets capable of trapping bacteria. In this new study, they found that these peptide nanonets have additional functionalities that can reduce the inflammation typically seen in response to bacterial infections. The nanonets showed anti-inflammatory efficacy by binding and entrapping gram-negative pathogen-released endotoxins and inflammation mediators produced by host macrophages. Because of the net charge difference between pro-inflammatory and anti-inflammatory cytokines, the nanonets exhibited a good preference for binding the former while minimally interacting with the latter.

In addition, the nanonets showed significant efficacy in reviving colistin’s (an antibiotic) antibacterial action against gram-negative infections, making it suitable for use as a last-resort treatment. This discovery is significant because it shows for the first time that multifunctional peptide nanonets can have far-reaching impacts in reducing sepsis complications at multiple stages. The peptide nanonets were able to lower the levels of pro-inflammatory cytokines that caused inflammation in the lungs of mice, which had been given endotoxins to damage their lungs. Moreover, the peptide nanonets were as effective as the drug dexamethasone, which is a steroidal drug used to relieve inflammation.

“As a multifunctional biomaterial for the integrative treatment of sepsis, our peptide-based nanonets have demonstrated exceptional therapeutic potential. Our long-term goal is to further develop these tools for clinical application”, said Rachel EE, Associate Professor Department of Pharmacy at the National University of Singapore, in an article published by EurekAlert. She is the corresponding author of the study.

This innovative research provides new options for addressing sepsis-related problems in healthcare. The selective trapping of endotoxins and pro-inflammatory cytokines by peptide nanonets is a major step forward. By simultaneously targeting the key components involved in the inflammatory response, these nanonets offer a more comprehensive approach to managing sepsis complications. As multifunctional anti-infective biomaterial, nanonets can be a promising option for restoring antibacterial efficacy against gram-negative pathogens.

The implications of this study’s findings for the treatment of sepsis are enormous. The research team continues to improve the peptide nanonets for clinical application. The multifunctional capabilities of these nanonets provide a promising avenue for future research and development in the field of biomaterials and targeted therapies.

Source: National University of Singapore ; Image: Adobe Stock

The article can be found at: Multifunctional Antibacterial Nanonets Attenuate Inflammatory Responses through Selective Trapping of Endotoxins and Pro-Inflammatory Cytokines.

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