Assessment of Anti-Tumor potential and safety of application of Glutathione stabilized Gold Nanoparticles conjugated with Chemotherapeutics

Int J Med Sci. 2020 Mar 12;17(6):824-833. doi: 10.7150/ijms.40827. eCollection 2020.

Abstract

Due to the high toxicity of currently used chemotherapeutics, novel methods of cancer treatment are needed. Gold nanoparticles (AuNPs) seem to be an interesting alternative due to penetration through biological membranes and systemic barriers. AuNPs as carriers of chemotherapeutics allow for reduced concentrations whilst maintaining the expected effect, and thus reducing the costs of therapy and adverse effects. We synthesized AuNPs stabilized with reduced glutathione (GSH) and conjugated with doxorubicin (DOX), gemcitabine (GEM) or cytarabine (CTA). This is the first study in which cytarabine-AuNPs were synthesized and characterized. Transmission electron microscopy (TEM), thermogravimetric analysis (TGA), nuclear magnetic resonance spectroscopy (NMR) and high-performance liquid chromatography (HPLC) were used to chemically characterize obtained nanoparticles. Antitumor activity and safety of application were assessed by MTT assay in in vitro model (human osteosarcoma cells -143B, human osteoblast- hFOB1.19, breast cancer cells - MCF7, breast epithelial cells - MCF10A, pancreatic cancer cells - PANC-1, and pancreatic cells - hTERT-HPNE cells). We have shown that cellular response varies according to the type and concentration of AuNPs. At some concentrations, we were able to show selective cytotoxicity of our AuNPs conjugates only to cancer cell lines. Synthesized nanoparticles were more cytotoxic to tumor cell lines than chemotherapeutics alone.

Keywords: Cancer; Chemotherapeutic; Drug deliver platform; Gold nanoparticles; Gold nanoparticles conjugate.

MeSH terms

  • Chromatography, High Pressure Liquid
  • Cytarabine / chemistry
  • Cytarabine / pharmacology
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / chemistry
  • Deoxycytidine / pharmacology
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Gemcitabine
  • Glutathione / chemistry
  • Glutathione / pharmacology*
  • Gold / adverse effects
  • Gold / chemistry*
  • Humans
  • MCF-7 Cells
  • Metal Nanoparticles / adverse effects
  • Metal Nanoparticles / chemistry*
  • Microscopy, Electron, Transmission
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Osteoblasts / drug effects
  • Telomerase / chemistry

Substances

  • Cytarabine
  • Deoxycytidine
  • Gold
  • Doxorubicin
  • TERT protein, human
  • Telomerase
  • Glutathione
  • Gemcitabine