Enhanced immunotherapy of SM5-1 in hepatocellular carcinoma by conjugating with gold nanoparticles and its in vivo bioluminescence tomographic evaluation

Biomaterials. 2016 May:87:46-56. doi: 10.1016/j.biomaterials.2016.02.007. Epub 2016 Feb 8.

Abstract

SM5-1 is a humanized mouse monoclonal antibody, targeting an over-expressed membrane protein of approximately 230 kDa in hepatocellular carcinoma (HCC). SM5-1 can be used for target therapy in hepatocellular carinoma due to its ability of inhibiting cell growth and inducing apoptosis. However, the tumor inhibition efficacy of SM5-1 in HCC cancer treatment remains low. In this study, we synthesized SM5-1-conjugated gold nanoparticles (Au-SM5-1 NPs) and investigated their anticancer efficacy in HCC both in vitro and in vivo. The tumor inhibition rates of Au-SM5-1 NPs for subcutaneous tumor mice were 40.10% ± 4.34%, 31.37% ± 5.12%, and 30.63% ± 4.87% on day 12, 18, and 24 post-treatment as determined by bioluminescent intensity. In addition, we investigated the antitumor efficacy of Au-SM5-1 NPs in orthotopic HCC tumor models. The results showed that the inhibition rates of Au-SM5-1 NPs can reach up to 39.64% ± 4.87% on day 31 post-treatment determined by the bioluminescent intensity of the abdomen in tumor-bearing mice. Furthermore, three-dimensional reconstruction results of the orthotopic tumor revealed that Au-SM5-1 NPs significantly inhibited tumor growth compared with SM5-1 alone. Our results suggested that the developed Au-SM5-1 NPs has great potential as an antibody-based nano-drug for HCC therapy.

Keywords: Antibody therapy; Bioluminescence tomography; Cell proliferation; Gold nanoparticles; Hepatocellular carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Carriers / chemistry*
  • Female
  • Gold / chemistry*
  • Humans
  • Liver / drug effects*
  • Liver / pathology*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / ultrastructure
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Drug Carriers
  • Gold