Intercellular pH-responsive histidine modified dextran-g-cholesterol micelle for anticancer drug delivery

• The histidine modified dextran-g-cholesterol micelles were successfully prepared.
• The micelles exhibited excellent pH-responsive behavior in acidic aqueous solution.
• Doxorubicin was effectively loaded into the micelles via hydrophobic interactions.
• The DOX release from all DOX-loaded micelles was accelerated in acid conditions.
• DOX-loaded micelles showed higher cellular proliferation inhibition.

Herein, the micelles based on histidine modified dextran-g-cholesterol (HDC) were successfully prepared which exhibited excellent pH-responsive behavior in acidic aqueous solution (pH < 6, within the range of malignant cellular endosome). Taking advantage of this pH-sensitivity in acidic conditions, doxorubicin (DOX), a model anticancer drug, was effectively loaded into the 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 also observed in MCF-7 cells. DOX-loaded pH-sensitive micelles showed higher cellular proliferation inhibition toward MCF-7 cells than that of pH-insensitive micelles. These features suggested that the micelles could efficiently load and deliver DOX into tumor cells, which can enhance the inhibition of cellular proliferation in vitro, providing a powerful mean for delivering and releasing cargoes at the tumor sites.

Figure optionsDownload as PowerPoint slide