title: Investigating photoexcitation-induced mitochondrial damage by chemotherapeutic corroles using multimode optical imaging.
abstract: We recently reported that a targeted, brightly fluorescent gallium corrole (HerGa) is highly effective for breast tumor detection and treatment. Unlike structurally similar porphryins, HerGa exhibits tumor-targeted toxicity without the need for photoexcitation. We have now examined whether photoexcitation further modulates HerGa toxicity, using multimode optical imaging of live cells, including two-photon excited fluorescence, differential interference contrast (DIC), spectral, and lifetime imaging. Using two-photon excited fluorescence imaging, we observed that light at specific wavelengths augments the HerGa-mediated mitochondrial membrane potential disruption of breast cancer cells in situ. In addition, DIC, spectral, and fluorescence lifetime imaging enabled us to both validate cell damage by HerGa photoexcitation and investigate HerGa internalization, thus allowing optimization of light dose and timing. Our demonstration of HerGa phototoxicity opens the way for development of new methods of cancer intervention using tumor-targeted corroles.
authors.affiliation: Minimally Invasive Surgical Technologies Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard D6061, Los Angeles, California 90048, USA.
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Hwang
authors.forename: David J
authors.initials: DJ
authors.lastname: Lubow
authors.forename: Jessica D
authors.initials: JD
authors.lastname: Sims
authors.forename: Harry B
authors.initials: HB
authors.lastname: Gray
authors.forename: Atif
authors.initials: A
authors.lastname: Mahammed
authors.forename: Zeev
authors.initials: Z
authors.lastname: Gross
authors.forename: Lali K
authors.initials: LK
authors.lastname: Medina-Kauwe
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Farkas
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D005708:Gallium / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D008856:Microscopy, Fluorescence / Q000379:methods; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D009942:Organometallic Compounds / Q000737:chemistry; D055668:Photochemical Processes / Q000187:drug effects / Q000528:radiation effects; D011166:Porphyrins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D009942:Organometallic Compounds; D011166:Porphyrins; C431863:corrole; C110932:tetramethyl rhodamine ethyl ester; D005708:Gallium