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

Hwang, Jae Youn; Lubow, David J.; Sims, Jessica D.; Gray, Harry B.; Mahammed, Atif; Gross, Zeev; Medina-Kauwe, Lali K.; Farkas, Daniel L.

doi:doi:10.1117/1.JBO.17.1.015003

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Journal of Biomedical Optics / Volume 17 / Issue 1 / Research Papers: General

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

J. Biomed. Opt. 17, 015003 (Feb 06, 2012); http://dx.doi.org/10.1117/1.JBO.17.1.015003

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Abstract

References (26)

Jae Youn Hwang and Daniel L. Farkas

Minimally Invasive Surgical Technologies Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard D6061, Los Angeles, California 90048

David J. Lubow, Jessica D. Sims, Lali K. Medina-Kauwe,

Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Boulevard D3059, Los Angeles, California 90048

Harry B. Gray

Beckman Institute, California Institute of Technology, Pasadena, California 91125

Atif Mahammed and Zeev Gross

Technion-Israel Institute of Technology, Schulish Faculty of Chemistry, Haifa 32000, Israel

University of California Los Angeles Geffen School of Medicine, Department of Medicine, Los Angeles, California 90048

University of Southern California, Department of Biomedical Engineering, , Los Angeles, California 90089

Spectral Molecular Imaging, Inc., Beverly Hills, California 90211

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.

History

Received Jul 22, 2011
Accepted Nov 08, 2011
Revised Nov 07, 2011
Published online Feb 06, 2012

Digital Object Identifier

http://dx.doi.org/10.1117/1.JBO.17.1.015003

Citation

Jae Youn Hwang, David J. Lubow, Jessica D. Sims, Harry B. Gray, Atif Mahammed, Zeev Gross, Lali K. Medina-Kauwe and Daniel L. Farkas, "Investigating photoexcitation-induced mitochondrial damage by chemotherapeutic corroles using multimode optical imaging", J. Biomed. Opt. 17, 015003 (Feb 06, 2012); http://dx.doi.org/10.1117/1.JBO.17.1.015003