Self-assembling peptide with dual function of cell penetration and antibacterial as a nano weapon to combat intracellular bacteria.

Intracellular bacterial infections and antimicrobial resistance are threatening global public health systems. Antimicrobial peptides are a potential solution to combat bacterial resistance, but the design of self-assembled nanopeptides with dual functions of cell penetration and antibacterial properties to combat intracellular bacteria remains a challenge. Here, we propose a strategy to develop self-assembled nanopeptides with dual functions through the chimerization of self-assembled core, hydrophobic motif, and cell-permeable unit. The optimal nanopeptides, F3FT and N3FT, exhibited potent antibacterial activity and excellent biocompatibility. Crucially, F3FT and N3FT are able to efficiently penetrate cells and eliminate intracellular bacteria and sniping inflammation. Moreover, F3FT and N3FT kill bacteria mainly by disrupting bacterial cell membranes and inducing excessive accumulation of reactive oxygen species. F3FT and N3FT have exhibited good safety and potent therapeutic potential in vivo. This scheme of constructing nanopeptides through multifunctional domains design provides a paradigm for dealing with escalating of intracellular bacteria and antimicrobial resistance.