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To improve the targeting efficacy of hyaluronic acid (HA)-based micelles, pH-sensitive mixed micelles based on HA-g-poly(L-histidine) (PHis) and d-α-tocopheryl polyethylene glycol 2000 copolymers were prepared and decorated with human epidermal growth factor receptor 2 (Her2) peptide, a tumor cell-specific peptide ligand, on their surface. The doxorubicin-loaded micelles (HA-PHis/peptide-d-α-tocopheryl polyethylene glycol 2000 mixed micelles [PHTM]) were characterized to have a unimodal size distribution and pH-dependent drug release pattern. In vitro tumor targeting studies demonstrated that PHTM exhibited the pronounced cytotoxicity and efficient internalization in MDA-MB-231 cells overexpressing CD44 and Her2 receptors. In vivo investigation into micelles in MDA-MB-231 tumor-bearing mice confirmed that PTHM could reach the tumor site more effectively and exert excellent tumor killing activity. In general, Her2 peptide decoration can enhance the selective cytotoxicity and antitumor activity of HA-based micelles.

Decoration of pH-sensitive copolymer micelles with tumor-specific peptide for enhanced cellular uptake of doxorubicin