Bioactive saccharide-conjugated polypeptide micelles for acid-triggered doxorubicin delivery

The synthesis and self-assembly of lactobionolactone-conjugated poly(l-glutamic acid)-b-poly(l-phenylalanine) amphiphilic block copolypeptides (Lac-PGA-b-PPhe) and their evaluation for anticancer drug doxorubicin (DOX) delivery have been investigated. Lactobionolactone was functionalized with the azide group and successfully conjugated with the terminal alkyne groups on the polypeptides through click reaction and these amphiphilic glycopolypeptides self-assembled to form micelles with bioactive galactose units on the particle surface as confirmed by selective lectin binding experiments. Drug release experiments showed that DOX released faster from saccharide-conjugated micelles under acidic conditions than under neutral conditions. The DOX-loaded, saccharide-conjugated micelles exhibited higher cytotoxicity toward HepG2 tumor cells than free DOX and saccharide-free micelles loaded with DOX at low concentrations, suggesting that the saccharide-conjugated micelles can effectively bind to the cells through specific recognition and subsequently the higher uptake of saccharide-conjugated micelles led to higher drug release and cytotoxicity under pH-sensitive conditions.