Photoexcitation of tumor-targeted corroles induces singlet oxygen-mediated augmentation of cytotoxicity

J Control Release. 2012 Nov 10;163(3):368-73. doi: 10.1016/j.jconrel.2012.09.015. Epub 2012 Oct 4.

Abstract

The tumor-targeted corrole particle, HerGa, displays preferential toxicity to tumors in vivo and can be tracked via fluorescence for simultaneous detection, imaging, and treatment. We have recently uncovered an additional feature of HerGa in that its cytotoxicity is enhanced by light irradiation. In the present study, we have elucidated the cellular mechanisms for HerGa photoexcitation-mediated cell damage using fluorescence optical imaging. In particular, we found that light irradiation of HerGa produces singlet oxygen, causing mitochondrial damage and cytochrome c release, thus promoting apoptotic cell death. An understanding of the mechanisms of cell death induced by HerGa, particularly under conditions of light-mediated excitation, may direct future efforts in further customizing this nanoparticle for additional therapeutic applications and enhanced potency.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / radiation effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • Humans
  • Light
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / physiology
  • Nanoparticles / administration & dosage*
  • Nanoparticles / radiation effects
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Porphyrins / administration & dosage*
  • Porphyrins / radiation effects
  • Singlet Oxygen*

Substances

  • Antineoplastic Agents
  • Porphyrins
  • corrole
  • Singlet Oxygen
  • Cytochromes c