Gold nanoparticles conjugated with cisplatin/doxorubicin/capecitabine lower the chemoresistance of hepatocellular carcinoma-derived cancer cells

J Gastrointestin Liver Dis. 2012 Jun;21(2):187-96.

Abstract

Background and aims: The aim of the current study was to evaluate in vitro the anti-tumor efficacy of gold nanoparticles (GNPs) conjugated with conventional chemotherapy drugs for the treatment of liver cancer. This approach based on gold proposes a novel platform therapy with minimal toxicity and increased efficacy profiles for the destruction of hepatic cancer cells.

Methods: GNPs, stabilized with a monolayer of L-aspartate and additional cytostatic drugs, were successfully used as a complex tumor-targeting drug-delivery system. The drugs (doxorubicin, cisplatin, and capecitabine) were non-covalently conjugated onto the hydrophilic assemblies of GNPs-L-Aspartate nanostructure. Transmission electron microscopy was used to characterize the morphological and structural properties of these drug-metallic nanostructures.

Results: The cellular proliferation rates in the presence of the anti-cancer drugs delivered by the GNPs were found to be statistically lower than those of cells exposed to the cytostatic drugs alone, indicating that GNPs facilitated an increased susceptibility of cancer cells to cisplatin, doxorubicin, and capecitabine plus ribavirin.

Conclusion: This approach could offer a new chemotherapy strategy for patients diagnosed with unresectable hepatocellular carcinoma (HCC).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Capecitabine
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / ultrastructure
  • Cell Death / drug effects
  • Cell Proliferation / drug effects
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacokinetics
  • Cisplatin / pharmacology
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacokinetics
  • Deoxycytidine / pharmacology
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology
  • Drug Delivery Systems / methods
  • Drug Resistance, Neoplasm
  • Drug Screening Assays, Antitumor / methods
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives
  • Fluorouracil / pharmacokinetics
  • Fluorouracil / pharmacology
  • Gold*
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / ultrastructure
  • Metal Nanoparticles*
  • Microscopy, Electron, Transmission
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Deoxycytidine
  • Capecitabine
  • Gold
  • Doxorubicin
  • Cisplatin
  • Fluorouracil