Graphene oxide-hydroxyapatite nanocomposites effectively deliver HSV-TK suicide gene to inhibit human breast cancer growth

J Biomater Appl. 2018 Aug;33(2):216-226. doi: 10.1177/0885328218788242.

Abstract

Gene therapy with herpes simplex virus thymidine kinase gene (HSV-TK), which is also known as "suicide" gene therapy, is effective in various tumor models. The lack of a safe and efficient gene delivery system has become a major obstacle to "suicide" gene therapy. In this study, the cytotoxicity and transfection efficiency of graphene oxide-hydroxyapatite (GO-Hap) were analyzed by MTS and flow cytometry, respectively. A series of assays were performed to evaluate the effects of GO-HAp/p-HRE/ERE-Sur-TK combined with ganciclovir treatment on growth of human breast normal and cancer cells. The results showed that GO-HAp nanocomposites effectively transfected cells with minimum toxicity. GO-HAp/p-HRE/ERE-Sur-TK combined with ganciclovir treatment inhibited the proliferation and induced cell apoptosis in cancer cells, while the cytotoxic effects are tolerable in normal breast cells. We conclude that the GO-HAp nanocomposites have significant potential as a gene delivery vector for cancer therapy.

Keywords: Breast cancer; GO–HAp; HSV-TK; gene therapy; nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Cell Line, Tumor
  • Durapatite / chemistry*
  • Female
  • Ganciclovir / pharmacology
  • Gene Transfer Techniques
  • Genes, Transgenic, Suicide
  • Genes, Viral
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / genetics
  • Genetic Vectors / pharmacology
  • Graphite / chemistry*
  • Humans
  • Nanocomposites / chemistry
  • Simplexvirus / enzymology*
  • Simplexvirus / genetics
  • Thymidine Kinase / genetics*
  • Transfection / methods

Substances

  • Antiviral Agents
  • graphene oxide
  • Graphite
  • Durapatite
  • Thymidine Kinase
  • Ganciclovir