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.