Gemini Surfactant-Like Peptide-Based Nanocages with Β-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., α-helix based coiled coils, β-sheet. Inspired by the robust protein fibril structures in amyloidosis, herein we constructed a β-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 ∼400 nm, which were robust enough even under both transmission electron microscopy and atomic force microscopy, indicating the significant contribution of β-sheet conformation. The β-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.