Synthesis and Biological Evaluation of Homogeneous Thiol-Linked NHC*-Au-Albumin and -Trastuzumab Bioconjugates

Chemistry. 2018 Aug 22;24(47):12250-12253. doi: 10.1002/chem.201800872. Epub 2018 May 22.

Abstract

Targeted delivery of potent cytotoxic drugs to cancer cells minimizes systemic toxicity and several side effects. NHC*-Au-Cl has already been proven to be a potent anticancer agent. In this study, we explore a strategy based on chemoselective cysteine conjugation of NHC*-Au-Cl to albumin and trastuzumab (Thiomab LC-V205C) to potentiate drug-ligand ratio, pharmacokinetics, as well as drug efficacy and safety. This strategy is a step forward towards the use of gold-based anticancer agents as targeted therapies.

Keywords: albumin; anticancer drug; drug delivery; gold(I) complex; targeted therapeutics.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cysteine / chemistry
  • Drug Carriers / chemistry
  • Gold / chemistry*
  • Half-Life
  • Humans
  • Imidazolines / chemistry*
  • Serum Albumin / chemistry*
  • Sulfhydryl Compounds / chemistry*
  • Trastuzumab / chemistry*
  • Trastuzumab / pharmacology

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Imidazolines
  • Serum Albumin
  • Sulfhydryl Compounds
  • Gold
  • Cysteine
  • Trastuzumab