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

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...

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Bibliographic Details
Published in:Journal of controlled release 2012-11, Vol.163 (3), p.368-373
Main Authors: Hwang, Jae Youn, Lubow, David J., Chu, David, Sims, Jessica, Alonso-Valenteen, Felix, Gray, Harry B., Gross, Zeev, Farkas, Daniel L., Medina-Kauwe, Lali K.
Format: Article
Language:English
Subjects:
A sulfonated gallium(III) corrole
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - radiation effects
apoptosis
Biological and medical sciences
Cell Line, Tumor
Cell Survival - drug effects
cytochrome c
Cytochromes c - metabolism
cytotoxicity
Drug delivery
fluorescence
General pharmacology
Humans
image analysis
irradiation
Light
Medical sciences
Membrane Potential, Mitochondrial - drug effects
Mitochondria - drug effects
Mitochondria - physiology
Nanoparticles
Nanoparticles - administration & dosage
Nanoparticles - radiation effects
neoplasms
Neoplasms - drug therapy
Neoplasms - metabolism
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Photoexcitation
Porphyrins - administration & dosage
Porphyrins - radiation effects
Singlet Oxygen
Tumor targeting
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Description
Summary: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. [Display omitted]
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2012.09.015