Pharmacological activity of DTPA linked to protein-based drug carrier systems

Biochem Biophys Res Commun. 2004 Oct 29;323(4):1236-40. doi: 10.1016/j.bbrc.2004.08.223.

Abstract

The chelating agent diethylenetriaminepentaacetic acid (DTPA) inhibits human cytomegalovirus replication. Since chelating agents are known to exhibit anti-cancer effects, DTPA-induced cytotoxicity was evaluated in breast cancer cells (MCF-7) and neuroblastoma cells (UKF-NB-3). DTPA inhibited cancer cell growth in threefold lower concentrations compared to human foreskin fibroblasts (HFF). Antiviral and anti-cancer activity of chelating agents is caused by intracellular complexation of metal ions. DTPA, an extracellular chelator, was covalently coupled to human serum albumin (HSA) molecules, HSA nanoparticles (HSA-NP), gelatin type B (GelB) molecules, and GelB nanoparticles (GelB-NP) to increase cellular uptake. Coupling of DTPA to drug carrier systems increased its cytotoxic and antiviral activity by 5- to 8-fold. Confocal laser scanning microscope examination revealed uptake of DTPA-HSA-NP in UKF-NB-3 cells and HFF. Therefore, coupling of DTPA to protein-based drug carrier systems increases its antiviral and anti-cancer activity probably by mediating cellular uptake.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Carriers / administration & dosage*
  • Drug Carriers / pharmacokinetics
  • Humans
  • Nanotubes / chemistry
  • Neuroblastoma / drug therapy
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology*
  • Particle Size
  • Pentetic Acid / administration & dosage*
  • Pentetic Acid / chemistry
  • Pentetic Acid / pharmacokinetics
  • Serum Albumin / administration & dosage
  • Serum Albumin / chemistry
  • Serum Albumin / pharmacokinetics*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Serum Albumin
  • Pentetic Acid