Antibacterial activities of physiologically stable, self-assembled peptide nanoparticles

In this study, we report that host defense protein-derived ten amino acid long disulfide-linked peptides self-assemble in the form of β-sheets and β-turns, and exhibit concentration-dependent self-assembly in the form of nanospheres, termed as disulfide linked nanospheres (DSNs). As expected, bare DSNs are prone to aggregation in ionic solutions and in the presence of serum proteins. To yield physiologically stable self-assembled peptide-based materials, DSNs are stabilized in the form of supramolecular assemblies using β-cyclodextrins (β-CD) and fucoidan, as delivery carriers. The inclusion complexes of DSNs with β-CD (β-CD-DSN) and electrostatic complexation of fucoidan with DSNs (FC-DSN) stabilizes the secondary structure of DSNs. Comparison of β-CD-DSNs with FC-DSNs reveals that inclusion complexes of DSNs formed in the presence of β-CD are highly stable under physiological conditions, show high cellular uptake, exhibit bacterial flocculation, and enhance antibacterial efficacies of DSNs in a range of Gram-positive and Gram-negative bacteria.