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

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

doi:10.1117/1.JBO.17.1.015003

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

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

Department of Electrical Engineering and Computer Science

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

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.

Original language	English
Article number	015003
Journal	Journal of Biomedical Optics
Volume	17
Issue number	1
DOIs	https://doi.org/10.1117/1.JBO.17.1.015003
State	Published - Jan 2012

Bibliographical note

Funding Information:
We thank Kevin Burton (Cedars-Sinai Medical Center) for providing valuable comments. This work was supported by grants from the U.S. Navy Bureau of Medicine and Surgery, the NIH (R21 CA116014, R01 CA140995, and R01 CA129822), the DoD (BC050662), the Susan G. Komen Breast Cancer foundation (BCTR0201194), and the Donna and Jesse Garber Award. Work at Caltech was supported by NIH DK019038 and the Arnold and Mabel Beckman Foundation. Work at the Technion was supported by The Herbert Irving Cancer and Atherosclerosis Research Fund and The United States-Israel Binational Science Foundation.

Keywords

FLIM
Gallium corrole
Mitochondrial membrane potential
Multimode optical imaging
Photoexcitation
Spectral
Two-photon excitation

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1117/1.JBO.17.1.015003

Cite this

@article{22604bb58a5242048ff9a09f99af0bde,

title = "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.",

keywords = "FLIM, Gallium corrole, Mitochondrial membrane potential, Multimode optical imaging, Photoexcitation, Spectral, Two-photon excitation",

author = "Hwang, {Jae Youn} and Lubow, {David J.} and Sims, {Jessica D.} and Gray, {Harry B.} and Atif Mahammed and Zeev Gross and Medina-Kauwe, {Lali K.} and Farkas, {Daniel L.}",

note = "Funding Information: We thank Kevin Burton (Cedars-Sinai Medical Center) for providing valuable comments. This work was supported by grants from the U.S. Navy Bureau of Medicine and Surgery, the NIH (R21 CA116014, R01 CA140995, and R01 CA129822), the DoD (BC050662), the Susan G. Komen Breast Cancer foundation (BCTR0201194), and the Donna and Jesse Garber Award. Work at Caltech was supported by NIH DK019038 and the Arnold and Mabel Beckman Foundation. Work at the Technion was supported by The Herbert Irving Cancer and Atherosclerosis Research Fund and The United States-Israel Binational Science Foundation.",

year = "2012",

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doi = "10.1117/1.JBO.17.1.015003",

language = "English",

volume = "17",

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AU - Hwang, Jae Youn

AU - Lubow, David J.

AU - Sims, Jessica D.

AU - Gray, Harry B.

AU - Mahammed, Atif

AU - Gross, Zeev

AU - Medina-Kauwe, Lali K.

AU - Farkas, Daniel L.

N1 - Funding Information: We thank Kevin Burton (Cedars-Sinai Medical Center) for providing valuable comments. This work was supported by grants from the U.S. Navy Bureau of Medicine and Surgery, the NIH (R21 CA116014, R01 CA140995, and R01 CA129822), the DoD (BC050662), the Susan G. Komen Breast Cancer foundation (BCTR0201194), and the Donna and Jesse Garber Award. Work at Caltech was supported by NIH DK019038 and the Arnold and Mabel Beckman Foundation. Work at the Technion was supported by The Herbert Irving Cancer and Atherosclerosis Research Fund and The United States-Israel Binational Science Foundation.

PY - 2012/1

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N2 - 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.

AB - 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.

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KW - Mitochondrial membrane potential

KW - Multimode optical imaging

KW - Photoexcitation

KW - Spectral

KW - Two-photon excitation

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

Abstract

Bibliographical note

Keywords

UN SDGs

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