title: Decoration of pH-sensitive copolymer micelles with tumor-specific peptide for enhanced cellular uptake of doxorubicin.
abstract: 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.
authors: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
authors: Qing
authors: Q
authors: Chen
authors: Department of Research and Development, Nanjing Chia Tai Tianqing Pharmaceutical Group Co. Ltd, Nanjing.
authors: Miaomiao
authors: M
authors: Long
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, People's Republic of China.
authors: Lipeng
authors: L
authors: Qiu
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, People's Republic of China.
authors: Mengqin
authors: M
authors: Zhu
authors: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
authors: Zhen
authors: Z
authors: Li
authors: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
authors: Mingxi
authors: M
authors: Qiao
authors: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
authors: Haiyang
authors: H
authors: Hu
authors: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
authors: Xiuli
authors: X
authors: Zhao
authors: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang.
authors: Dawei
authors: D
authors: Chen
mesh_terms: D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry* / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008823:Micelles; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D024502:alpha-Tocopherol / Q000737:chemistry
chemical_list: D004317:Doxorubicin; D004337:Drug Carriers; D006639:Histidine; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D008823:Micelles; D010455:Peptides; D011092:Polyethylene Glycols; D018719:Erb-b2 Receptor Tyrosine Kinases; D024502:alpha-Tocopherol; C033223:polyhistidine; C508053:ERBB2 protein, human
keywords: Her2 peptide; antitumor efficacy; hyaluronic acid; poly(L-histidine); targeted delivery