Gemini surfactant-like peptide-based nanocages with beta-sheet-enhanced stability and encapsulation efficiency of hydrophobic anticancer drugs

Peptide-based scaffolds have been widely applied to drug delivery because of their ease and high yields of synthesis, well-defined structure, biocompatibility, diversity, tunability of properties, and molecular recognition abilities. However, the stability of peptide-based nanostructures highly depends on the intermolecular assembling manner, e.g., alpha-helix based coiled coils, beta-sheet. Inspired by the robust protein fibril structures in amyloidosis, herein we constructed a beta-sheet-forming gemini surfactant-like peptide to self-assemble into nanocages with the help of molecular dynamics simulation. As expected, the experimental results showed that nanocages can be formed with the inner diameter of up to similar to 400 nm, which were robust enough even under both transmission electron microscopy and atomic force microscopy, indicating the significant contribution of beta-sheet conformation. The beta-nanocages can load hydrophobic anticancer drugs, e.g., paclitaxel with a very high encapsulation efficiency, which holds great potential for clinic drug delivery due to the improved anticancer effect as compared with paclitaxel alone.