title: Cellular uptake and cytotoxicity of a near-IR fluorescent corrole-TiO2 nanoconjugate.
abstract: We are investigating the biological and biomedical imaging roles and impacts of fluorescent metallocorrole-TiO2 nanoconjugates as potential near-infrared optical contrast agents in vitro in cancer and normal cell lines. The TiO2 nanoconjugate labeled with the small molecule 2,17-bis(chlorosulfonyl)-5,10,15-tris(pentafluorophenyl)corrolato aluminum(III) (1-Al-TiO2) was prepared. The nanoparticle 1-Al-TiO2 was characterized by transmission electron microscopy (TEM) and integrating-sphere electronic absorption spectroscopy. TEM images of three different samples of TiO2 nanoparticles (bare, H2O2 etched, and 1-Al functionalized) showed similarity in shapes and sizes with an average diameter of 29nm for 1-Al-TiO2. Loading of 1-Al on the TiO2 surfaces was determined to be ca. 20-40mg 1-Al/g TiO2. Confocal fluorescence microscopy (CFM) studies of luciferase-transfected primary human glioblastoma U87-Luc cells treated with the nanoconjugate 1-Al-TiO2 as the contrast agent in various concentrations were performed. The CFM images revealed that 1-Al-TiO2 was found inside the cancer cells even at low doses (0.02-2μg/mL) and localized in the cytosol. Bioluminescence studies of the U87-Luc cells exposed to various amounts of 1-Al-TiO2 showed minimal cytotoxic effects even at higher doses (2-2000μg/mL) after 24h. A similar observation was made using primary mouse hepatocytes (PMH) treated with 1-Al-TiO2 at low doses (0.0003-3μg/mL). Longer incubation times (after 48 and 72h for U87-Luc) and higher doses (>20μg/mL 1-Al-TiO2 for U87-Luc and >3μg/mL 1-Al-TiO2 for PMH) showed decreased cell viability.
authors: Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Carl M
authors: CM
authors: Blumenfeld
authors: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Bryce F
authors: BF
authors: Sadtler
authors: Cellular Imaging Core, The Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine of USC, Los Angeles, CA 90027, USA.
authors: G Esteban
authors: GE
authors: Fernandez
authors: Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine of USC, Los Angeles, CA 90089, USA.
authors: Lily
authors: L
authors: Dara
authors: Department of Biological Sciences, Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90068, USA; Translational Biomedical Imaging Laboratory, Department of Radiology, The Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine of USC, Los Angeles, CA 90027, USA.
authors: Cathie
authors: C
authors: Nguyen
authors: Department of Biological Sciences, Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90068, USA.
authors: Felix
authors: F
authors: Alonso-Valenteen
authors: Department of Biological Sciences, Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90068, USA.
authors: Lali
authors: L
authors: Medina-Kauwe
authors: Translational Biomedical Imaging Laboratory, Department of Radiology, The Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine of USC, Los Angeles, CA 90027, USA.
authors: Rex A
authors: RA
authors: Moats
authors: Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Nathan S
authors: NS
authors: Lewis
authors: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Robert H
authors: RH
authors: Grubbs
authors: Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: hbgray@caltech.edu.
authors: Harry B
authors: HB
authors: Gray
authors: Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Translational Biomedical Imaging Laboratory, Department of Radiology, The Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine of USC, Los Angeles, CA 90027, USA. Electronic address: ksorasaenee@chla.usc.edu.
authors: Karn
authors: K
authors: Sorasaenee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D006801:Humans; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D049329:Nanostructures / Q000633:toxicity; D011166:Porphyrins / Q000737:chemistry*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D014025:Titanium / Q000737:chemistry*
chemical_list: D011166:Porphyrins; C431863:corrole; C009495:titanium dioxide; D014025:Titanium
keywords: Cellular uptake; Corrole; Cytotoxic effect; Fluorescence; Nanoconjugate; TiO(2) nanoparticle