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.
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA. jaeyhwan@usc.edu
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Hwang
authors.forename: David J
authors.initials: DJ
authors.lastname: Lubow
authors.forename: David
authors.initials: D
authors.lastname: Chu
authors.forename: Jessica
authors.initials: J
authors.lastname: Sims
authors.forename: Felix
authors.initials: F
authors.lastname: Alonso-Valenteen
authors.forename: Harry B
authors.initials: HB
authors.lastname: Gray
authors.forename: Zeev
authors.initials: Z
authors.lastname: Gross
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Farkas
authors.forename: Lali K
authors.initials: LK
authors.lastname: Medina-Kauwe
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D008027:Light; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D053758:Nanoparticles / Q000008:administration & dosage* / Q000528:radiation effects; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011166:Porphyrins / Q000008:administration & dosage* / Q000528:radiation effects; D026082:Singlet Oxygen
chemical_list: D000970:Antineoplastic Agents; D011166:Porphyrins; C431863:corrole; D026082:Singlet Oxygen; D045304:Cytochromes c