title: Gold nanoparticles and radiofrequency in experimental models for hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is one of the most lethal and chemo-refractory cancers, clearly, alternative treatment strategies are needed. We utilized 10nm gold nanoparticles as a scaffold to synthesize nanoconjugates bearing a targeting antibody (cetuximab, C225) and gemcitabine. Loading efficiency of gemcitabine on the gold nanoconjugates was 30%. Targeted gold nanoconjugates in combination with RF were selectively cytotoxic to EGFR expressing Hep3B and SNU449 cells when compared to isotype particles with/without RF (P<0.05). In animal experiments, targeted gold nanoconjugates halted the growth of subcutaneous Hep3B xenografts in combination with RF exposure (P<0.05). These xenografts also demonstrated increased apoptosis, necrosis and decreased proliferation compared to controls. Normal tissues were unharmed. We have demonstrated that non-invasive RF-induced hyperthermia when combined with targeted delivery of gemcitabine is more effective and safe at dosages ~275-fold lower than the current clinically-delivered systemic dose of gemcitabine.
  
  
  BACKGROUND
  In a model of hepatocellular carcinoma, the authors demonstrate that non-invasive RF-induced hyperthermia applied with cetuximab targeted delivery of Au NP-gemcitabine conjugate is more effective and safe at dosages ~ 275-fold lower than the current clinically-used systemic dose of gemcitabine.
authors.affiliation: Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Raoof
authors.affiliation: Department of Surgery, Baylor College of Medicine, Houston, TX, USA; Department of Chemistry and Richard E. Smalley Institute for Nanoscale Science & Technology, Rice University, Houston, TX, USA.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Corr
authors.affiliation: Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Cihui
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Surgery, Baylor College of Medicine, Houston, TX, USA; Department of Chemistry and Richard E. Smalley Institute for Nanoscale Science & Technology, Rice University, Houston, TX, USA.
authors.forename: Brandon T
authors.initials: BT
authors.lastname: Cisneros
authors.affiliation: Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Warna D
authors.initials: WD
authors.lastname: Kaluarachchi
authors.affiliation: Department of Surgery, Baylor College of Medicine, Houston, TX, USA; Department of Chemistry and Richard E. Smalley Institute for Nanoscale Science & Technology, Rice University, Houston, TX, USA.
authors.forename: Sophia
authors.initials: S
authors.lastname: Phounsavath
authors.affiliation: Department of Chemistry and Richard E. Smalley Institute for Nanoscale Science & Technology, Rice University, Houston, TX, USA.
authors.forename: Lon J
authors.initials: LJ
authors.lastname: Wilson
authors.affiliation: Department of Surgery, Baylor College of Medicine, Houston, TX, USA; Department of Mechanical Engineering and Materials Science Rice University, Houston, TX, USA. Electronic address: steven.curley@bcm.edu.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Curley
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D000068818:Cetuximab; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006046:Gold / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D006979:Hyperthermia, Induced; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D053768:Metal Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D008807:Mice, Inbred BALB C; D058726:Nanoconjugates / Q000737:chemistry / Q000627:therapeutic use*; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058726:Nanoconjugates; D003841:Deoxycytidine; D006046:Gold; D000068818:Cetuximab; D000093542:Gemcitabine
keywords: Gemcitabine; Hepatocellular; Hyperthermia; Nanoparticle; Radiofrequency