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

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.

• Authors: Jae Youn Hwang, David J Lubow, Jessica D Sims, Harry B Gray, Atif Mahammed, Zeev Gross, Lali K Medina-Kauwe, Daniel L Farkas
• Journal: Journal of biomedical optics (J Biomed Opt) Vol. 17 Issue 1 Pg. 015003 (Jan 2012) ISSN: 1560-2281 [Electronic] United States
• PMID: 22352647 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

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

Topics

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