Multi-Functional Synthetic Peptide Nanonets for Bacterial Infections

Pharmaceutical scientists from Singapore State University (NUS) has produced multifunctional synthetic peptide nanonets to reduce inflammation due to bacterial infections. This is achieved by trapping bacterial endotoxins and pro-inflammatory cytokines together.

Schematic illustrating the proposed anti-inflammatory mechanism of fibrillation peptides: (1) Entrapment of endotoxin by nanonets; (2) Cytokine capture by nanonets; and (3) Intracellular effects by soluble peptide molecules. Image Credit: Advanced Health Care Ingredients

Endotoxemia is the presence of endotoxins in the blood. Gram negative pathogens, eg E. coli, releases these endotoxins during systemic infection. The host inflammatory response can cause extensive tissue damage and septic shock if left unchecked. This response is associated with a high mortality rate.

In the past, previous studies have been largely unsuccessful due to the complicated nature of the communication between anti- and pro-inflammatory mediators.

For better management of septic complications, newer techniques concentrate on multi-cytokines. A study group led by Associate Professor Rachel EE from the Department of Pharmacy, NUS, determined that antibacterial peptide nanonets can reduce the inflammatory response commonly associated with bacterial infections.

These results were developed on previous reports on the design of anti-microbial peptides that have the ability to self-assemble in situ into bacterial trapping nanonets. The anti-inflammatory activity is possible because of the capacity of the nanonets to trap and bind to endotoxins released by gram-negative pathogens and inflammatory mediators produced by host macrophages.

Interestingly, cationic nanonets selectively entrap proinflammatory cytokines at the same time, little bind anti-inflammatory cytokines. The researchers succeeded in this by exploiting the difference in total net charge between these two groups of various cytokines.

These results are reported in the journal Advanced Health Care Ingredients.

The lipopolysaccharide (LPS) binding effect leads to the restoration of the antimicrobial activity of colistin, a last-line therapy, against gram-negative pathogens. Remarkably, this is the first published case of multi-functional peptide nanonets with long-term effects in reducing septic complexity damage at multiple stages.

Biological examination of the peptide nanonets with the use of an acute lung injury model established their efficiency in minimizing proinflammatory cytokine levels in the bronchoalveolar fluid of an endotoxin-inoculated murine model. The peptide effect produced is analogous to the control drug dexamethasone.

Prof Ee concluded, “Our peptide-based nanonets have demonstrated unique therapeutic potential as multifunctional biomaterials for holistic management of sepsis. Going forward, we hope to continue its optimization for clinical use.

Journal Reference

Tram, NDT, et al. (2023). The multifunctional antibacterial nanonets attenuate the inflammatory response through selective trapping of proinflammatory endotoxins and cytokines. Advanced Health Care Ingredients.


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