title: pH-Responsive Hyaluronic Acid-Based Mixed Micelles for the Hepatoma-Targeting Delivery of Doxorubicin.
abstract: The tumor targetability and stimulus responsivity of drug delivery systems are crucial in cancer diagnosis and treatment. In this study, hepatoma-targeting mixed micelles composed of a hyaluronic acid-glycyrrhetinic acid conjugate and a hyaluronic acid-l-histidine conjugate (HA-GA/HA-His) were prepared through ultrasonic dispersion. The formation and characterization of the mixed micelles were confirmed via ¹H-NMR, particle size, and ζ potential measurements. The in vitro cellular uptake of the micelles was evaluated using human liver carcinoma (HepG2) cells. The antitumor effect of doxorubicin (DOX)-loaded micelles was investigated in vitro and in vivo. Results indicated that the DOX-loaded HA-GA/HA-His micelles showed a pH-dependent controlled release and were remarkably absorbed by HepG2 cells. Compared with free DOX, the DOX-loaded HA-GA/HA-His micelles showed a higher cytotoxicity to HepG2 cells. Moreover, the micelles effectively inhibited tumor growth in H22 cell-bearing mice. These results suggest that the HA-GA/HA-His mixed micelles are a good candidate for drug delivery in the prevention and treatment of hepatocarcinoma.
authors.affiliation: School of Bioscience and Technology, Weifang Medical University, Wei Fang 261053, Shandong, China. jlwu2008@163.com.
authors.forename: Jing-Liang
authors.initials: JL
authors.lastname: Wu
authors.affiliation: School of Bioscience and Technology, Weifang Medical University, Wei Fang 261053, Shandong, China. gxtian2008@163.com.
authors.forename: Gui-Xiang
authors.initials: GX
authors.lastname: Tian
authors.affiliation: School of Bioscience and Technology, Weifang Medical University, Wei Fang 261053, Shandong, China. yuwjwf@163.com.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Yu
authors.affiliation: School of Bioscience and Technology, Weifang Medical University, Wei Fang 261053, Shandong, China. guangtaojia@163.com.
authors.forename: Guang-Tao
authors.initials: GT
authors.lastname: Jia
authors.affiliation: School of Bioscience and Technology, Weifang Medical University, Wei Fang 261053, Shandong, China. swgch@wfmc.edu.cn.
authors.forename: Tong-Yi
authors.initials: TY
authors.lastname: Sun
authors.affiliation: School of Bioscience and Technology, Weifang Medical University, Wei Fang 261053, Shandong, China. zhiqingao2013@163.com.
authors.forename: Zhi-Qin
authors.initials: ZQ
authors.lastname: Gao
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D056945:Hep G2 Cells; D006639:Histidine / Q000737:chemistry; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D014183:Transplantation, Heterologous
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008823:Micelles; D006639:Histidine; D004317:Doxorubicin; D006820:Hyaluronic Acid
keywords: glycyrrhetinic acid; hepatoma-targeting; hyaluronic acid; micelle