title: Transferrin modified graphene oxide for glioma-targeted drug delivery: in vitro and in vivo evaluations.
abstract: Transferrin (Tf), an iron-transporting serum glycoprotein that binds to receptors overexpressed at the surface of glioma cells, was chosen as the ligand to develop Tf-conjugated PEGylated nanoscaled graphene oxide (GO) for loading and glioma targeting delivery of anticancer drug doxorubicin (Dox) (Tf-PEG-GO-Dox). Tf-GO with lateral dimensions of 100-400 nm exhibited a Dox loading ratio up to 115.4%. Compared with Dox-loaded PEGylated GO (PEG-GO-Dox) and free Dox, Tf-PEG-GO-Dox displayed greater intracellular delivery efficiency and stronger cytotoxicity against C6 glioma cells. A competition test showed that Tf was essential to glioma targeting in vitro. The HPLC assay for Dox concentration in tumor tissue and contrapart tissue of the brain demonstrated that Tf-PEG-GO-Dox could deliver more Dox into tumor in vivo. The life span of tumor bearing rats after the administration of Tf-PEG-GO-Dox was extended significantly compared to the rats treated with saline, Dox, and PEG-GO-Dox. In conclusion, we developed Tf-PEG-GO-Dox which exhibited significantly improved therapeutic efficacy for glioma both in vitro and in vivo.
authors.affiliation: Neurosurgery Department, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Liu
authors.forename: He
authors.initials: H
authors.lastname: Shen
authors.forename: Jinning
authors.initials: J
authors.lastname: Mao
authors.forename: Liming
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Jiang
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001667:Binding, Competitive; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006108:Graphite / Q000737:chemistry*; D008297:Male; D049329:Nanostructures; D036103:Nanotechnology / Q000379:methods; D009368:Neoplasm Transplantation; D010087:Oxides / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014168:Transferrin / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D010087:Oxides; D014168:Transferrin; D006108:Graphite; D004317:Doxorubicin