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

Abstract

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 were shown to selectively entrap the negatively charged LPS and pro-inflammatory cytokines TNF-α and IL-6. This in turn enabled 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, we demonstrated that intratracheal administration of the fibrillating peptides was effective at lowering local release of TNF-α and IL-6. Together with previously shown ability to simultaneously trap and kill pathogenic bacteria, our peptide nanonets display remarkable potential as a holistic, multifunctional anti-infective and anti-septic biomaterial. This article is protected by copyright. All rights reserved.