Cellular uptake and cytotoxicity of a near-IR fluorescent corrole-TiO2 nanoconjugate

Carl M Blumenfeld; Bryce F Sadtler; G Esteban Fernandez; Lily Dara; Cathie Nguyen; Felix Alonso-Valenteen; Lali Medina-Kauwe; Rex A Moats; Nathan S Lewis; Robert H Grubbs; Harry B Gray; Karn Sorasaenee

doi:10.1016/j.jinorgbio.2014.06.015

Cellular uptake and cytotoxicity of a near-IR fluorescent corrole-TiO2 nanoconjugate

J Inorg Biochem. 2014 Nov:140:39-44. doi: 10.1016/j.jinorgbio.2014.06.015. Epub 2014 Jun 28.

Authors

Affiliations

¹ Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
² Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
³ Cellular Imaging Core, The Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine of USC, Los Angeles, CA 90027, USA.
⁴ Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine of USC, Los Angeles, CA 90089, USA.
⁵ 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.
⁶ Department of Biological Sciences, Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90068, USA.
⁷ 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.
⁸ 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: [email protected].
⁹ 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: [email protected].

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.

Keywords: Cellular uptake; Corrole; Cytotoxic effect; Fluorescence; Nanoconjugate; TiO(2) nanoparticle.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Cells, Cultured
Hepatocytes / cytology
Hepatocytes / drug effects
Humans
Mice
Microscopy, Electron, Transmission
Microscopy, Fluorescence
Nanostructures* / toxicity
Porphyrins / chemistry*
Spectroscopy, Near-Infrared / methods*
Titanium / chemistry*

Substances

Porphyrins
corrole
titanium dioxide
Titanium

Abstract

Publication types

MeSH terms

Substances

Grants and funding