title: Cholesteryl hyaluronic acid-coated, reduced graphene oxide nanosheets for anti-cancer drug delivery.
abstract: Here, we report hyaluronyl reduced graphene oxide (rGO) nanosheets as a tumor-targeting delivery system for anticancer agents. Hyaluronyl-modified rGO nanosheets were prepared by synthesizing cholesteryl hyaluronic acid (CHA) and using it to coat rGO nanosheets, yielding CHA-rGO. Compared with rGO, CHA-rGO nanosheets showed increased colloidal stability under physiological conditions and improved in vivo safety, with a survival rate of 100% after intravenous administration of 40 mg/kg in mice. The doxorubicin (Dox) loading capacity of CHA-rGO was 4-fold greater than that of rGO. Uptake of Dox by CD44-overexpressing KB cells was higher for CHA-rGO than for rGO, and was decreased in the presence of hyaluronic acid through competition for CD44 receptor binding. After intravenous administration in tumor-bearing mice, CHA-rGO/Dox showed higher tumor accumulation than rGO/Dox. The in vivo antitumor efficacy of Dox delivered by CHA-rGO was significantly increased compared with free Dox or rGO/Dox. In CHA-rGO/Dox-treated mice, tumor weights were reduced to 14.1% ± 0.1% of those in untreated mice. Our findings indicate that CHA-rGO nanosheets possess greater stability, safety, drug-loading capacity, and CD44-mediated delivery of Dox than rGO nanosheets. These beneficial properties of CHA-rGO improved the distribution of Dox to tumors and facilitated the cellular uptake of Dox by CD44-overexpressing tumor cells, resulting in enhanced anticancer effects.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Miao
authors.forename: Gayong
authors.initials: G
authors.lastname: Shim
authors.forename: Choong Mo
authors.initials: CM
authors.lastname: Kang
authors.forename: Soondong
authors.initials: S
authors.lastname: Lee
authors.forename: Yearn Seong
authors.initials: YS
authors.lastname: Choe
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D006820:Hyaluronic Acid / Q000031:analogs & derivatives*; D007624:KB Cells; D051379:Mice; D049329:Nanostructures / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010084:Oxidation-Reduction; D010087:Oxides / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D018960:Hyaluronan Receptors; D010087:Oxides; D006108:Graphite; D004317:Doxorubicin; D006820:Hyaluronic Acid
keywords: Anti-tumor effect; Doxorubicin; Graphene-based nanosheets; Hyaluronic acid