Intracellular pH-sensitive supramolecular amphiphiles based on host–guest recognition between benzimidazole and β-cyclodextrin as potential drug delivery vehicles

Abstract

Intracellular pH-sensitive supramolecular block amphiphiles based on the host–guest interaction between benzimidazole (BM) modified poly(ε-caprolactone) (BM-PCL) and cyclodextrin (β-CD) terminated dextran (Dex-β-CD) were designed. The supramolecular block amphiphiles could further self-assemble into supramolecular micelles and exhibit pH-sensitive behaviour in acidic aqueous solution when the pH value was below 6. Doxorubicin (DOX), a model anticancer drug, was effectively loaded into the supramolecular micelles via hydrophobic interactions. The DOX release from all DOX-loaded micelles was accelerated in acid conditions mimicking the endosomal/lysosomal compartments. The enhanced intracellular DOX release was observed in HepG2 cells. DOX-loaded intracellular pH-sensitive supramolecular micelles showed higher cellular proliferation inhibition towards HepG2 cells than pH-insensitive micelles. These features suggested that the supramolecular micelles could efficiently load and deliver DOX into tumor cells and enhance the inhibition of cellular proliferation in vitro, providing a powerful mean for delivering and releasing cargoes at the tumor sites.