Multifunctional Antibacterial Nanonets Attenuate Inflammatory Responses through Selective Trapping of Endotoxins and Pro-Inflammatory Cytokines

Extracellular lipopolysaccharide (LPS) released from bacteria cells can enter the bloodstream and cause septic complications with excessive host inflammatory responses. Target-specific strategies to inactivate inflammation mediators have largely failed to improve the prognosis of septic patients in clinical trials. By utilizing their high density of positive charges, de novo designed peptide nanonets are shown to selectively entrap the negatively charged LPS and pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). This in turn enables the nanonets to suppress LPS-induced cytokine production by murine macrophage cell line and rescue the antimicrobial activity of the last-resort antibiotic, colistin, from LPS binding. Using an acute lung injury model in mice, it is demonstrated that intratracheal administration of the fibrillating peptides is effective at lowering local release of TNF-alpha and IL-6. Together with previously shown ability to simultaneously trap and kill pathogenic bacteria, the peptide nanonets display remarkable potential as a holistic, multifunctional anti-infective, and anti-septic biomaterial.

Automated summary

Due to the failure of target-specific strategies, a novel multifunctional biomaterial based on peptide nanonets has been developed to selectively trap lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in order to suppress inflammation and restore the antimicrobial activity of the last-resort antibiotic colistin. In addition to its ability to simultaneously trap and kill bacteria, the peptide nanonets have shown remarkable potential as a holistic anti-infective and anti-septic biomaterial.