title: Transferrin-modified Doxorubicin-loaded biodegradable nanoparticles exhibit enhanced efficacy in treating brain glioma-bearing rats.
abstract: Doxorubicin (Dox) is widely used for the treatment of solid tumors but its clinical utility on glioma is limited. In this study, we developed a novel nano-scale drug delivery system employing biodegradable nanoparticle (NP) as carriers to load Dox. Transferrin (Tf) was conjugated to the surface of NP to specifically target the NP to glioma. Tf-NP-Dox was prepared via emulsification-solvent evaporation method, and characterized for the size, Drug loading capacity (DLC), entrapment efficiency, and Tf number on the surface. The antitumor efficiency in vitro was evaluated via CCK-8 assay. The transmembrane transportation was evaluated via HPLC assay. The antitumor efficiency in vivo was assessed in C6 glioma intracranial implant rat model. The average diameter of Tf-NP-Dox was 100 nm with ∼32 Tf molecules on the surface. DLC was 4.4%. CCK-8 assay demonstrated much stronger cytotoxicity of Tf-NP-Dox to C6 glioma cells compared to NP-Dox or Dox. HPLC assay showed that Tf-NP-Dox transported Dox into C6 cells with high efficiency. In vivo, Tf-NP-Dox could transport Dox into tumors compare to contralateral part, with tumor inhibitory ratio and survival higher than NP-Dox or Dox. Taken together, our results suggest that Tf-NP-Dox exhibits better therapeutic effects against glioma both in vitro and in vivo, and is a potential nano-scale drug delivery system for glioma chemotherapy.
authors.affiliation: 1 Neurosurgery Department, The Second Affiliated Hospital of Soochow University , Suzhou, China .
authors.forename: Guodong
authors.initials: G
authors.lastname: Liu
authors.forename: Jinning
authors.initials: J
authors.lastname: Mao
authors.forename: Zirong
authors.initials: Z
authors.lastname: Jiang
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Hu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Jiang
authors.forename: Caiyuan
authors.initials: C
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Dong
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials / Q000737:chemistry*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D004705:Endocytosis; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D051381:Rats; D012997:Solvents / Q000737:chemistry; D014168:Transferrin / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D012997:Solvents; D014168:Transferrin; D004317:Doxorubicin