title: The intratumoral administration of ferucarbotran conjugated with doxorubicin improved therapeutic effect by magnetic hyperthermia combined with pharmacotherapy in a hepatocellular carcinoma model.
abstract: BACKGROUND
  Local hyperthermia of tumor in conjunction with chemotherapy is a promising strategy for cancer treatment. The aim of this study was to evaluate the efficacy of intratumoral delivery of clinically approved magnetic nanoparticles (MNPs) conjugated with doxorubicin to simultaneously induce magnetic hyperthermia and drug delivery in a hepatocellular carcinoma (HCC) model.
  
  
  METHODS
  HCC cells expressing luciferase were implanted into the flank of BALB/c-nu mice (n = 19). When the tumor diameter reached 7-8 mm, the animals were divided into four groups according to the injected agents: group A (normal saline, n = 4), group B (doxorubicin, n = 5), group C (MNP, n = 5), and group D (MNP/doxorubicin complex, n = 5). Animals were exposed to an alternating magnetic field (AMF) to receive magnetic hyperthermia, and intratumoral temperature changes were measured.
  
  
  RESULTS
  The rise in temperature of the tumors was 1.88 ± 0.21°C in group A, 0.96 ± 1.05°C in B, 7.93 ± 1.99°C in C, and 8.95 ± 1.31°C in D. The RSI of the tumors at day 14 post-treatment was significantly lower in group D (0.31 ± 0.20) than in group A (2.23 ± 1.14), B (0.94 ± 0.47), and C (1.02 ± 0.21). The apoptosis rates of the tumors were 11.52 ± 3.10% in group A, 23.0 ± 7.68% in B, 25.4 ± 3.36% in C, and 39.0 ± 13.2% in D, respectively.
  
  
  CONCLUSIONS
  The intratumoral injection of ferucarbotran conjugated with doxorubicin shows an improved therapeutic effect compared with doxorubicin or ferucarbotran alone when the complex is injected into HCC tissues exposed to AMF for magnetic hyperthermia. This strategy of combining doxorubicin and MNP-induced magnetic hyperthermia exhibits a synergic effect on inhibiting tumor growth in an HCC model.
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Jeon
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Ahn
authors.forename: Hyeonjin
authors.initials: H
authors.lastname: Kim
authors.forename: In Jae
authors.initials: IJ
authors.lastname: Chung
authors.forename: Seulhee
authors.initials: S
authors.lastname: Jung
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Kim
authors.forename: Hyewon
authors.initials: H
authors.lastname: Youn
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Chung
authors.forename: Young Il
authors.initials: YI
authors.lastname: Kim
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003911:Dextrans / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D015552:Injections, Intralesional; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D008163:Luminescent Measurements; D058185:Magnetite Nanoparticles / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
chemical_list: D003911:Dextrans; D058185:Magnetite Nanoparticles; D004317:Doxorubicin; C065507:ferumoxides