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Published November 2014 | Supplemental Material + Accepted Version
Journal Article Open

Cellular uptake and cytotoxicity of a near-IR fluorescent corrole–TiO_2 nanoconjugate


We are investigating the biological and biomedical imaging roles and impacts of fluorescent metallocorrole–TiO_2 nanoconjugates as potential near-infrared optical contrast agents in vitro in cancer and normal cell lines. The TiO_2 nanoconjugate labeled with the small molecule 2,17-bis(chlorosulfonyl)-5,10,15-tris(pentafluorophenyl)corrolato aluminum(III) (1-Al–TiO_2) was prepared. The nanoparticle 1-Al–TiO_2 was characterized by transmission electron microscopy (TEM) and integrating-sphere electronic absorption spectroscopy. TEM images of three different samples of TiO_2 nanoparticles (bare, H_2O_2 etched, and 1-Al functionalized) showed similarity in shapes and sizes with an average diameter of 29 nm for 1-Al–TiO_2. Loading of 1-Al on the TiO_2 surfaces was determined to be ca. 20–40 mg 1-Al/g TiO_2. Confocal fluorescence microscopy (CFM) studies of luciferase-transfected primary human glioblastoma U87-Luc cells treated with the nanoconjugate 1-Al–TiO_2 as the contrast agent in various concentrations were performed. The CFM images revealed that 1-Al–TiO_2 was found inside the cancer cells even at low doses (0.02–2 μg/mL) and localized in the cytosol. Bioluminescence studies of the U87-Luc cells exposed to various amounts of 1-Al–TiO_2 showed minimal cytotoxic effects even at higher doses (2–2000 μg/mL) after 24 h. A similar observation was made using primary mouse hepatocytes (PMH) treated with 1-Al–TiO_2 at low doses (0.0003–3 μg/mL). Longer incubation times (after 48 and 72 h for U87-Luc) and higher doses (> 20 μg/mL 1-Al–TiO_2 for U87-Luc and > 3 μg/mL 1-Al–TiO_2 for PMH) showed decreased cell viability.

Additional Information

© 2014 Elsevier Inc. Received 13 March 2014, Revised 19 June 2014, Accepted 20 June 2014, Available online 28 June 2014. We thank the CHLA Radiology Endowment Fund (K.S.), Sanofi (H.B.G.), Doheny Eye Institute (R.H.G.), and Beckman Institute Postdoctoral Fellowship (B.F.S.) for the support. We also thank Anahit Hovsepyan, Seda Mkhitaryan, Vazgen Khankaldyyan, and Gevorg Karapetyan for the help with the bioluminescence assays. Absorption measurements and profilometry were performed at the Molecular Materials Research Center, Beckman Institute, Caltech. We thank Carol M. Garland for the assistance in TEM imaging. B.F.S. and N.S.L. acknowledge the support from the "Light–Material Interactions in Energy Conversion" Energy Frontier Research Center funded by the US Department of Energy, Office of Science, Office of Basic Energy Sciences (DE-SC0001293).

Attached Files

Accepted Version - nihms811177.pdf

Supplemental Material - mmc1.docx

Supplemental Material - mmc2.zip


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