The ligand exchange of citrates to thioabiraterone on gold nanoparticles for prostate cancer therapy

Int J Pharm. 2020 Jun 15:583:119319. doi: 10.1016/j.ijpharm.2020.119319. Epub 2020 Apr 20.

Abstract

Cancer is one of the leading causes of morbidity and mortality worldwide and nanotechnology has a significant potential to enhance the therapeutic and diagnostic performance of anti-cancer agents. Our work offers a simple and feasible strategy for thiocompound nanomedicines to be used in cancer therapy. Novel gold nanoparticles conjugated with thioabiraterone (AuNP-S-AB) were synthesized and significant new analytical methodologies were developed for their characterization by UV-Vis, TEM, IR, NMR and TGA. Our synthetic approach was based on the ligand exchange of citrates to thioabiraterone on gold nanoparticles. The average particle size of AuNP-S-AB was 14.5 nm with a spherical shape. The identity of thioabiraterone on the gold nanoparticles was proved by NMR and IR spectroscopy. The coverage of the gold nanoparticles with 40.9% (m/m) thioabiraterone was calculated from a TGA analysis. Molecular interactions between the thiol group of thioabiraterone and gold nanoparticles were evaluated through a combined experimental and theoretical study using the density functional theory (DFT). Additionally, an experiment conducted on hepatocytes or human prostate epithelial cells proved that newly synthesized thiol forms of abiraterone, as well as AuNP-S-AB, are more biocompatible than abiraterone. Our proposed idea of delivering abiraterone with our newly designed AuNP-S-AB may constitute a promising and novel prospect in cancer therapy.

Keywords: AuNPs-gold nanoparticles; DFT – density functional theory; HS-AB - thiolated abiraterone (thioabiraterone); HepG2 cells; PNT-2 cells.

MeSH terms

  • Androstenes / administration & dosage
  • Androstenes / chemistry*
  • Cell Line
  • Cell Survival / drug effects
  • Citrates / administration & dosage
  • Citrates / chemistry*
  • Epithelial Cells / drug effects
  • Gold / administration & dosage
  • Gold / chemistry*
  • Humans
  • Ligands
  • Liver / cytology
  • Male
  • Metal Nanoparticles / administration & dosage
  • Metal Nanoparticles / chemistry*
  • Prostate / cytology
  • Prostatic Neoplasms / drug therapy
  • Sulfhydryl Compounds / administration & dosage
  • Sulfhydryl Compounds / chemistry*

Substances

  • Androstenes
  • Citrates
  • Ligands
  • Sulfhydryl Compounds
  • Gold
  • abiraterone