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

• Published in: Advanced healthcare materials Vol. 12; no. 20; pp. e2203232 - n/a
• Main Authors: Tram, Nhan Dai Thien, Tran, Quy Thi Ngoc, Xu, Jian, Su, Jeannie Ching Ting, Liao, Wupeng, Wong, Wai Shiu Fred, Ee, Pui Lai Rachel
• Format: Journal Article
• Language: English
• Published: Germany 01.08.2023
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; anti‐infective; anti‐septics; Cytokines; Endotoxins; inflammation; Interleukin-6 - metabolism; Lipopolysaccharides - pharmacology; Mice; nanostructures; peptides; Tumor Necrosis Factor-alpha - metabolism; anti-septics; peptides; anti-infective; inflammation; nanostructures
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202203232

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‐α (TNF‐α) 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‐α 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. Strategies to inactivate individual cytokines have largely failed to improve the clinical outcomes of septic patients. Peptide nanonets selectively entrap endotoxins and multiple pro‐inflammatory cytokines via electrostatic interactions. They suppress cytokine production by macrophages both in vitro and in vivo. They also rescue the antimicrobial activity of colistin from endotoxin binding. These peptide nanonets show promises as a multifunctional anti‐infective biomaterial.