title: Hyaluronic acid-decorated graphene oxide nanohybrids as nanocarriers for targeted and pH-responsive anticancer drug delivery.
abstract: A novel nanohybrid of hyaluronic acid (HA)-decorated graphene oxide (GO) was fabricated as a targeted and pH-responsive drug delivery system for controlling the release of anticancer drug doxorubicin (DOX) for tumor therapy. For the preparation, DOX was first loaded onto GO nanocarriers via π-π stacking and hydrogen-bonding interactions, and then it was decorated with HA to produce HA-GO-DOX nanohybrids via H-bonding interactions. In this strategy, HA served as both a targeting moiety and a hydrophilic group, making the as-prepared nanohybrids targeting, stable, and disperse. A high loading efficiency (42.9%) of DOX on the nanohybrids was also obtained. Cumulative DOX release from HA-GO-DOX was faster in pH 5.3 phosphate-buffered saline solution than that in pH 7.4, providing the basis for pH-response DOX release in the slightly acidic environment of tumor cells, while the much-slower DOX release from HA-GO-DOX than DOX showed the sustained drug-release capability of the nanohybrids. Fluorescent images of cellular uptake and cell viability analysis studies illustrated that these HA-GO-DOX nanohybrids significantly enhanced DOX accumulation in HA-targeted HepG2 cancer cells compared to HA-nontargeted RBMEC cells and subsequently induced selective cytotoxicity to HepG2 cells. In vivo antitumor efficiency of HA-GO-DOX nanohybrids showed obviously enhanced tumor inhibition rate for H22 hepatic cancer cell-bearing mice compared with free DOX and the GO-DOX formulation. These studies suggest that the HA-GO-DOX nanohybrids have potential clinical applications for anticancer drug delivery.
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University); Ministry of Education, College of Pharmaceutical Sciences, Southwest University , Chongqing, 400715, People's Republic of China.
authors.forename: Erqun
authors.initials: E
authors.lastname: Song
authors.forename: Weiye
authors.initials: W
authors.lastname: Han
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Cheng
authors.forename: Lingrui
authors.initials: L
authors.lastname: Li
authors.forename: Lichao
authors.initials: L
authors.lastname: Liu
authors.forename: Guizhi
authors.initials: G
authors.lastname: Zhu
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.forename: Weihong
authors.initials: W
authors.lastname: Tan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D002470:Cell Survival; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006108:Graphite / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D053761:Nanocomposites / Q000737:chemistry*; D036103:Nanotechnology; D009369:Neoplasms / Q000188:drug therapy*; D010087:Oxides / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000970:Antineoplastic Agents; D010087:Oxides; D006108:Graphite; D004317:Doxorubicin; D006820:Hyaluronic Acid