Facile design of gemini surfactant-like peptide for hydrophobic drug delivery and antimicrobial activity

Native gemini surfactant-like conformation of APK is caused by two prolines as the intrinsic turn-forming unit and the peptide could self-assemble to form nanosheets or nanofibers, which could be used as hydrophobic drug carrier with antimicrobial activity. [Display omitted] Recently, many kinds of gemini-type amphiphilic peptides have been designed and shown their advantage as self-assembling nanomaterials. In this study, we proposed a simple strategy to design gemini surfactant-like peptides, which are only composed of natural amino acids and can be easily obtained by conventional peptide sythnesis. Taking two prolines as the turn-forming units, a peptide named APK was designed. The petide has a linear sequence but naturally takes the conformation like a gemini surfactant. Compared with a single-tailed surfactant-like peptide A6K, APK showed much stronger ability to undergo self-assembly and to encapsulate hydrophobic pyrene. Several hydrophobic drugs including paclitaxel, doxorubicin, etomidate and propofol were encapsulated by APK, and the corresponding formulations showed anti-tumor or anesthetic efficacy comparable to their respective clinical formulations. Furthermore, APK could inhibit the growth of different microorganisms including E. coli, S. aureus and C. albicans. Etomidate and propofol formulations encapsulated by APK also showed strong antimicrobial activity. Taking APK as an example, our study indicated a straightforward strategy to design gemini surfactant-like peptides, which could be potential nanomaterials for exploring hydrophobic drug formulations with efficacy, safety and self-antimicrobial activity.