Cooperative effect of 5-aminolevulinic acid and gold nanoparticles for photodynamic therapy of cancer

J Pharm Sci. 2013 Aug;102(8):2760-9. doi: 10.1002/jps.23621. Epub 2013 May 27.

Abstract

An enhanced capacity for protoporphyrin IX (PpIX) synthesis through 5-aminolevulinic acid (ALA) administration has been reported in cancer cells. We compared the effect of ALA and ALA combined with gold nanoparticles (ALA-AuNPs) for photodynamic therapy (PDT) on human cervical cancer cell line. Because PpIX after photoactivation produces reactive oxygen species (ROS), ALA-AuNPs combinations can enhance this production and then induce higher phototoxicity. With this aim, two different-sized AuNPs (14 and 136 nm, AuNP1 and AuNP2, respectively) were successfully synthesized and characterized by UV-visible spectrophotometry and transmission electron microscopy. AuNPs were combined with ALA to evaluate their cooperative action in the intracellular ROS production, cell viability, and cell death mechanism. Results showed that ALA-AuNPs combinations induced cell death via ROS-mediated apoptosis after PDT. When exposed to light at their resonance wavelength, AuNP2 combined with ALA result in cytotoxicity and cell injury in greater extension than ALA and ALA-AuNP1 combination.

Keywords: ALA; ROS; apoptosis; cytotoxicity; gold nanoparticle; photodynamic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminolevulinic Acid / pharmacology*
  • Apoptosis / drug effects
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cervix Uteri / drug effects
  • Cervix Uteri / metabolism
  • Cervix Uteri / pathology
  • Drug Synergism
  • Female
  • Gold / chemistry
  • Gold / pharmacology*
  • Humans
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Photochemotherapy
  • Photosensitizing Agents / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • Photosensitizing Agents
  • Reactive Oxygen Species
  • Gold
  • Aminolevulinic Acid