Tailoring supramolecular antimicrobial peptides: from self-assembled nanoarchitectures to activities

The emergence of antibiotic-resistant bacteria has become a major threat to global public health and has prompted the discovery of antibiotic alternatives. Natural antimicrobial peptides (AMPs) confer a unique non-specific membrane rupture mechanism, showing great potential in killing drug-resistant bacteria. However, natural AMPs have certain weaknesses, including stability and toxicity issues, which seriously hinder their in vivo applications. Synthetic AMPs possess similar characteristics to natural AMPs, including positive charges, amphiphilicity, and the ability to fold into diverse secondary structures. These properties are essential for AMPs penetration into membranes, allowing them to exhibit antimicrobial effects. Moreover, supramolecular self-assembly, facilitated by hydrophobic interaction, hydrogen bonding, π-π stacking, and electrostatic interaction, can generate nanoparticles, nanotubes, nanofibers, and hydrogels with well-defined nanoarchitectures. Utilizing peptide self-assembly to form various nanoarchitectures is an effective approach for generating antibacterial nanomaterials, offering potential advantages such as enhanced antibacterial properties, improved stability, and reduced cytotoxicity. This review highlights recent advancements in tailoring supramolecular AMPs to create diverse nano-architectures for combating infectious diseases.