Gold nanoparticles and radiofrequency in experimental models for hepatocellular carcinoma

Mustafa Raoof, Stuart J. Corr, Cihui Zhu, Brandon T. Cisneros, Warna D. Kaluarachchi, Sophia Phounsavath, Lon J. Wilson, Steven A. Curley

Research output: Contribution to journalArticlepeer-review

Abstract

Hepatocellular carcinoma (HCC) is one of the most lethal and chemo-refractory cancers, clearly, alternative treatment strategies are needed. We utilized 10. nm 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. From the Clinical Editor: 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.

Original languageEnglish (US)
Pages (from-to)1121-1130
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume10
Issue number6
DOIs
StatePublished - Aug 2014

Keywords

  • Gemcitabine
  • Hepatocellular
  • Hyperthermia
  • Nanoparticle
  • Radiofrequency

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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