Multifunctional Antibacterial Nanonets Attenuate Inflammatory Responses through Selective Trapping of Endotoxins and...

Area of Science:

• Biomaterials Science
• Infectious Diseases
• Immunology

Background:

• Extracellular lipopolysaccharide (LPS) from bacteria can cause septic complications due to excessive host inflammatory responses.
• Current strategies targeting inflammation mediators have shown limited success in improving septic patient outcomes.
• LPS can interfere with the efficacy of antibiotics like colistin.

Purpose of the Study:

• To investigate the potential of de novo designed peptide nanonets as a multifunctional anti-infective and anti-septic biomaterial.
• To evaluate the ability of peptide nanonets to entrap LPS and pro-inflammatory cytokines.
• To assess the therapeutic efficacy of peptide nanonets in reducing inflammation and enhancing antibiotic activity.

Main Methods:

• Designed peptide nanonets with a high density of positive charges to selectively entrap negatively charged LPS and cytokines (TNF-α, IL-6).
• Tested the ability of nanonets to suppress LPS-induced cytokine production in a murine macrophage cell line.
• Evaluated the rescue of colistin's antimicrobial activity from LPS binding by the nanonets.
• Utilized an acute lung injury mouse model to assess the effect of intratracheal peptide nanonet administration on local cytokine release.

Main Results:

• Peptide nanonets effectively entrapped LPS and pro-inflammatory cytokines (TNF-α, IL-6).
• Nanonets suppressed LPS-induced cytokine production and rescued colistin's antimicrobial activity.
• Intratracheal administration of peptide nanonets reduced local TNF-α and IL-6 levels in an acute lung injury model.
• The peptide nanonets demonstrated simultaneous bacterial trapping and killing capabilities.

Conclusions:

• De novo designed peptide nanonets show significant potential as a multifunctional anti-infective and anti-septic biomaterial.
• These nanonets offer a holistic strategy to combat infection by trapping pathogens, neutralizing endotoxins, and modulating host inflammatory responses.
• The demonstrated efficacy in preclinical models suggests a promising therapeutic avenue for sepsis and related complications.