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Investigating the photosensitizer-potential of targeted gallium corrole using multimode optical imaging

Hwang, Jae Youn and Lubow, Jay and Chu, David and Gross, Zeev and Gray, Harry B. and Farkas, Daniel L. and Medina-Kauwe, Lali K. (2011) Investigating the photosensitizer-potential of targeted gallium corrole using multimode optical imaging. In: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XX. Proceedings of SPIE. No.7886. Society of Photo-Optical Instrumentation Engineers , Bellingham, WA, Art. No. 78860M. ISBN 9780819484239. PMCID PMC4445411. http://resolver.caltech.edu/CaltechAUTHORS:20161028-124138808

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Abstract

We recently developed a novel therapeutic particle, HerGa, for breast cancer treatment and detection. HerGa consists of a tumor-targeted cell penetration protein noncovalently assembled with a gallium-metallated corrole. The corrole is structurally similar to porphyrin, emits intense fluorescence, and has proven highly effective for breast tumor treatment preclinically, without light exposure. Here, we tested HerGa as a photosensitizer for photodynamic therapy and investigated its mechanism of action using multimode optical imaging. Using confocal fluorescence imaging, we observed that HerGa disrupts the mitochondrial membrane potential in situ, and this disruption is substantially augmented by light exposure. In addition, spectral and fluorescence lifetime imaging were utilized to both validate the mitochondrial membrane potential disruption and investigate HerGa internalization, allowing us to optimize the timing for light dosimetry. We observed, using advanced multimode optical imaging, that light at a specific wavelength promotes HerGa cytotoxicity, which is likely to cause disruption of mitochondrial function. Thus, we can identify for the first time the capacity of HerGa as a photosensitizer for photodynamic therapy and reveal its mechanism of action, opening possibilities for therapeutic intervention in human breast cancer management.


Item Type:Book Section
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1117/12.873337DOIArticle
http://proceedings.spiedigitallibrary.org/proceeding.aspx?articleid=732477PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445411/PubMed CentralArticle
Additional Information:© 2011 SPIE. This work was supported by grants from the NIH (R21 CA116014, R01 CA102126, R01 CA129822, and R01 CA140995), 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. Partial support from the US Navy Bureau of Medicine and Surgery is gratefully acknowledged. LKMK wishes to thank JC, MMK, and DR for ongoing support.
Funders:
Funding AgencyGrant Number
NIHR21 CA116014
NIHR01 CA102126
NIHR01 CA129822
NIHR01 CA140995
Department of DefenseBC050662
Susan G. Komen Breast Cancer FoundationBCTR0201194
Donna and Jesse Garber AwardUNSPECIFIED
NIHDK019038
Arnold and Mabel Beckman FoundationUNSPECIFIED
Herbert Irving Cancer and Atherosclerosis Research FundUNSPECIFIED
U.S. Navy Bureau of Medicine and SurgeryUNSPECIFIED
Subject Keywords:Multimode optical imaging, targeted gallium corrole, photosensitizers, spectral imaging, fluorescence lifetime imaging
PubMed Central ID:PMC4445411
Record Number:CaltechAUTHORS:20161028-124138808
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20161028-124138808
Official Citation:Jae Youn Hwang ; Jay Lubow ; David Chu ; Zeev Gross ; Harry B. Gray ; Daniel L. Farkas ; Lali K. Medina-Kauwe; Investigating the photosensitizer-potential of targeted gallium corrole using multimode optical imaging. Proc. SPIE 7886, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XX, 78860M (February 17, 2011); doi:10.1117/12.873337
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:71578
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:28 Oct 2016 19:53
Last Modified:28 Oct 2016 19:53

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