Photoexcitation of tumor-targeted corroles induces singlet oxygen-mediated augmentation of cytotoxicity

Jae Youn Hwang; David J. Lubow; David Chu; Jessica Sims; Felix Alonso-Valenteen; Harry B. Gray; Zeev Gross; Daniel L. Farkas; Lali K. Medina-Kauwe

doi:10.1016/j.jconrel.2012.09.015

Photoexcitation of tumor-targeted corroles induces singlet oxygen-mediated augmentation of cytotoxicity

Jae Youn Hwang, David J. Lubow, David Chu, Jessica Sims, Felix Alonso-Valenteen, Harry B. Gray, Zeev Gross, Daniel L. Farkas, Lali K. Medina-Kauwe

Department of Electrical Engineering and Computer Science

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

56 Scopus citations

Abstract

The tumor-targeted corrole particle, HerGa, displays preferential toxicity to tumors in vivo and can be tracked via fluorescence for simultaneous detection, imaging, and treatment. We have recently uncovered an additional feature of HerGa in that its cytotoxicity is enhanced by light irradiation. In the present study, we have elucidated the cellular mechanisms for HerGa photoexcitation-mediated cell damage using fluorescence optical imaging. In particular, we found that light irradiation of HerGa produces singlet oxygen, causing mitochondrial damage and cytochrome c release, thus promoting apoptotic cell death. An understanding of the mechanisms of cell death induced by HerGa, particularly under conditions of light-mediated excitation, may direct future efforts in further customizing this nanoparticle for additional therapeutic applications and enhanced potency.

Original language	English
Pages (from-to)	368-373
Number of pages	6
Journal	Journal of Controlled Release
Volume	163
Issue number	3
DOIs	https://doi.org/10.1016/j.jconrel.2012.09.015
State	Published - 10 Nov 2012

Bibliographical note

Funding Information:
This work was supported by grants from the NIH ( R01 CA140995 , and R01 CA129822 ). 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

A sulfonated gallium(III) corrole
Drug delivery
Nanoparticles
Photoexcitation
Singlet oxygen
Tumor targeting

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10.1016/j.jconrel.2012.09.015

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title = "Photoexcitation of tumor-targeted corroles induces singlet oxygen-mediated augmentation of cytotoxicity",

abstract = "The tumor-targeted corrole particle, HerGa, displays preferential toxicity to tumors in vivo and can be tracked via fluorescence for simultaneous detection, imaging, and treatment. We have recently uncovered an additional feature of HerGa in that its cytotoxicity is enhanced by light irradiation. In the present study, we have elucidated the cellular mechanisms for HerGa photoexcitation-mediated cell damage using fluorescence optical imaging. In particular, we found that light irradiation of HerGa produces singlet oxygen, causing mitochondrial damage and cytochrome c release, thus promoting apoptotic cell death. An understanding of the mechanisms of cell death induced by HerGa, particularly under conditions of light-mediated excitation, may direct future efforts in further customizing this nanoparticle for additional therapeutic applications and enhanced potency.",

keywords = "A sulfonated gallium(III) corrole, Drug delivery, Nanoparticles, Photoexcitation, Singlet oxygen, Tumor targeting",

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

note = "Funding Information: This work was supported by grants from the NIH ( R01 CA140995 , and R01 CA129822 ). 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",

month = nov,

day = "10",

doi = "10.1016/j.jconrel.2012.09.015",

language = "English",

volume = "163",

pages = "368--373",

journal = "Journal of Controlled Release",

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T1 - Photoexcitation of tumor-targeted corroles induces singlet oxygen-mediated augmentation of cytotoxicity

AU - Hwang, Jae Youn

AU - Lubow, David J.

AU - Chu, David

AU - Sims, Jessica

AU - Alonso-Valenteen, Felix

AU - Gray, Harry B.

AU - Gross, Zeev

AU - Farkas, Daniel L.

AU - Medina-Kauwe, Lali K.

N1 - Funding Information: This work was supported by grants from the NIH ( R01 CA140995 , and R01 CA129822 ). 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 - 2012/11/10

Y1 - 2012/11/10

N2 - The tumor-targeted corrole particle, HerGa, displays preferential toxicity to tumors in vivo and can be tracked via fluorescence for simultaneous detection, imaging, and treatment. We have recently uncovered an additional feature of HerGa in that its cytotoxicity is enhanced by light irradiation. In the present study, we have elucidated the cellular mechanisms for HerGa photoexcitation-mediated cell damage using fluorescence optical imaging. In particular, we found that light irradiation of HerGa produces singlet oxygen, causing mitochondrial damage and cytochrome c release, thus promoting apoptotic cell death. An understanding of the mechanisms of cell death induced by HerGa, particularly under conditions of light-mediated excitation, may direct future efforts in further customizing this nanoparticle for additional therapeutic applications and enhanced potency.

AB - The tumor-targeted corrole particle, HerGa, displays preferential toxicity to tumors in vivo and can be tracked via fluorescence for simultaneous detection, imaging, and treatment. We have recently uncovered an additional feature of HerGa in that its cytotoxicity is enhanced by light irradiation. In the present study, we have elucidated the cellular mechanisms for HerGa photoexcitation-mediated cell damage using fluorescence optical imaging. In particular, we found that light irradiation of HerGa produces singlet oxygen, causing mitochondrial damage and cytochrome c release, thus promoting apoptotic cell death. An understanding of the mechanisms of cell death induced by HerGa, particularly under conditions of light-mediated excitation, may direct future efforts in further customizing this nanoparticle for additional therapeutic applications and enhanced potency.

KW - A sulfonated gallium(III) corrole

KW - Drug delivery

KW - Nanoparticles

KW - Photoexcitation

KW - Singlet oxygen

KW - Tumor targeting

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DO - 10.1016/j.jconrel.2012.09.015

M3 - Article

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AN - SCOPUS:84867744682

SN - 0168-3659

VL - 163

SP - 368

EP - 373

JO - Journal of Controlled Release

JF - Journal of Controlled Release

IS - 3

ER -

Photoexcitation of tumor-targeted corroles induces singlet oxygen-mediated augmentation of cytotoxicity

Abstract

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Keywords

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