title: Magnetic polycarbonate microspheres for tumor-targeted delivery of tumor necrosis factor.
abstract: OBJECTIVE
  The specific expression of transferrin receptor can represent a diagnostic tool or therapeutic target in solid tumors expressing this antigen. Herein, the human transferrin receptor monoclonal antibody (T9) was investigated as a tumor-targeting group for active targeted-drug delivery systems.
  
  
  METHODS
  A tumor-targeted conjugate T9-TNF was synthesized by the attachment of both human transferrin receptor monoclonal antibody (T9) as a tumor-targeting group and human tumor necrosis factor-α (TNF) as an anti-cancer drug to two terminated hydroxyl groups of poly(ethylene glycol). Subsequently, a solvent evaporation technique was adopted to produce anti-cancer magnetic polymer microspheres T9-TNF-PC-M containing T9-TNF and Fe3O4 magnetic ultrafine powders (M) using poly(trimethylene carbonate-co-5,5-dimethyl trimethylene carbonate) (PC, P(TMC-co-DTC)) as a polymeric carrier.
  
  
  CONCLUSIONS
  These magnetic polycarbonate microspheres possessed a steady TNF release rate in phosphate buffer saline solution, strong magnetic responsiveness and high T9-TNF loading capacity. In vitro cytotoxicity assays demonstrated the microspheres T9-TNF-PC-M and conjugate T9-TNF were strongly inhibitory to the human hepatic carcinoma (Bel-7204) cells. In vivo site-specific therapy in nude mice with human hepatic carcinoma indicated that the microspheres T9-TNF-PC-M and conjugate T9-TNF possessed markedly higher anti-tumor activity against Bel-7204 in mice than that of TNF.
  
  
  CONCLUSIONS
  These results indicated that the magnetic polycarbonate microspheres were suitable as the potential-targeted treatment for hepatic carcinoma therapeutics.
authors.affiliation: School of Material Science and Engineering, Wuhan Institute of Technology , Wuhan , People's Republic of China .
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Du
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Yan
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wu
authors.forename: Chang-Lie
authors.initials: CL
authors.lastname: Fan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D052203:Ferrosoferric Oxide / Q000737:chemistry*; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008280:Magnetics; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008863:Microspheres; D011076:Polycarboxylate Cement / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011990:Receptors, Transferrin / Q000276:immunology / Q000378:metabolism; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D047368:Tumor Burden / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004337:Drug Carriers; D018796:Immunoconjugates; D011076:Polycarboxylate Cement; D011990:Receptors, Transferrin; D014409:Tumor Necrosis Factor-alpha; C005506:polycarbonate; D011092:Polyethylene Glycols; D052203:Ferrosoferric Oxide