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

Hwang, Jae Youn and Farkas, Daniel L. and Lubow, David J. and Sims, Jessica D. and Medina-Kauwe, Lali K. and Gray, Harry B. and Mahammed, Atif and Gross, Zeev (2012) Investigating photoexcitation-induced mitochondrial damage by chemotherapeutic corroles using multimode optical imaging. Journal of Biomedical Optics, 17 (1). Art. No. 015003. ISSN 1083-3668. PMCID PMC3380813.

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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.

Item Type:Article
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URLURL TypeDescription DOIArticle CentralArticle
Gray, Harry B.0000-0002-7937-7876
Additional Information:© 2012 SPIE. Paper 11395P received Jul. 22, 2011; revised manuscript received Nov. 7, 2011; accepted for publication Nov. 8, 2011; published online Feb. 6, 2012. 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.
Funding AgencyGrant Number
U.S. Navy Bureau of Medicine and SurgeryUNSPECIFIED
NIHR21 CA116014
NIHR01 CA140995
NIHR01 CA129822
Department of Defense (DoD)BC050662
Susan G. Komen Breast Cancer FoundationBCTR0201194
Donna and Jesse Garber AwardUNSPECIFIED
Arnold and Mabel Beckman FoundationUNSPECIFIED
Herbert Irving Cancer and Atherosclerosis Research FundUNSPECIFIED
Binational Science Foundation (USA-Israel)UNSPECIFIED
Subject Keywords:multimode optical imaging; spectral; FLIM; gallium corrole; two-photon excitation; mitochondrial membrane potential; photoexcitation
Issue or Number:1
PubMed Central ID:PMC3380813
Record Number:CaltechAUTHORS:20120412-133338394
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Official 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);
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:30069
Deposited By: Tony Diaz
Deposited On:17 Apr 2012 18:30
Last Modified:22 Nov 2019 09:58

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