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

• Published in: Journal of controlled release Vol. 163; no. 3; pp. 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: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 10.11.2012; Elsevier
• 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; Nanoparticles; Drug delivery; Singlet oxygen; Tumor targeting; A sulfonated gallium(III) corrole; Photoexcitation; Oxygen; Pharmaceutical technology; Targeting; Nanoparticle; A sulfonated gilium(III) corrole; Cytotoxicity; Drug carrier; Malignant tumor; Target; Microparticle; Cancer
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2012.09.015

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]