Investigating photoexcitation-induced mitochondrial damage by chemotherapeutic corroles using multimode optical imaging

J Biomed Opt. 2012 Jan;17(1):015003. doi: 10.1117/1.JBO.17.1.015003.

Abstract

We recently reported that a targeted, brightly fluorescent gallium corrole (HerGa) is highly effective for breast tumor detection and treatment. Unlike structurally similar porphryins, HerGa exhibits tumor-targeted toxicity without the need for photoexcitation. We have now examined whether photoexcitation further modulates HerGa toxicity, using multimode optical imaging of live cells, including two-photon excited fluorescence, differential interference contrast (DIC), spectral, and lifetime imaging. Using two-photon excited fluorescence imaging, we observed that light at specific wavelengths augments the HerGa-mediated mitochondrial membrane potential disruption of breast cancer cells in situ. In addition, DIC, spectral, and fluorescence lifetime imaging enabled us to both validate cell damage by HerGa photoexcitation and investigate HerGa internalization, thus allowing optimization of light dose and timing. Our demonstration of HerGa phototoxicity opens the way for development of new methods of cancer intervention using tumor-targeted corroles.

Publication types

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

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacokinetics
  • Fluorescent Dyes / pharmacology*
  • Gallium / chemistry
  • Gallium / pharmacokinetics
  • Gallium / pharmacology*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potential, Mitochondrial / radiation effects
  • Microscopy, Fluorescence / methods
  • Mitochondria / drug effects*
  • Mitochondria / pathology
  • Mitochondria / radiation effects*
  • Organometallic Compounds / chemistry
  • Photochemical Processes / drug effects
  • Photochemical Processes / radiation effects
  • Porphyrins / chemistry
  • Porphyrins / pharmacokinetics
  • Porphyrins / pharmacology*

Substances

  • Antineoplastic Agents
  • Fluorescent Dyes
  • Organometallic Compounds
  • Porphyrins
  • corrole
  • tetramethyl rhodamine ethyl ester
  • Gallium