Multifunctional Antibacterial Nanonets Attenuate Inflammatory Responses through Selective Trapping of
Endotoxins and Pro-Inflammatory Cytokines
Nhan Dai Thien Tram, Quy Thi Ngoc Tran, Jian Xu, Jeannie Ching Ting Su, Wupeng Liao, Wai Shiu Fred Wong, and Pui Lai Rachel Ee*
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.