Cellular Uptake and Organ Accumulation of Amphipolar Metallocorroles with Cytoprotective and Cytotoxic Properties

Zoya      Okun; Lana      Kupershmidt; Moussa      B. H. Youdim; Zeev      Gross

doi:10.2174/187152011795677535

Abstract

We report here an investigation that focuses on the organ distribution of metal complexes that are chelated by the amphipolar corrole whose macrocycle is decorated by two sulphonic acid head groups, which are emerging potential therapeutics against cancer (the cytotoxic Ga chelate) and diseases that are characterized by excessive production of ROS and RNS (the cytoprotective Mn and Fe derivatives). We show that the intraperitoneally injected fluorescent gallium(III) derivative accumulates in tissues sections of the kidney, liver, lung, heart, and pancreas. It also reaches the brain blood vessels, but does not cross the blood brain barrier. These findings are of prime importance for future in vivo studies on disease models, as they point toward a large utility of this kind of corrole chelates for treating cancer, neurodegenerative diseases characterized by “leaking BBB”, cardiovascular diseases and diabetes.

Keywords: Imaging, oxidative stress, bioavailability, bio-distribution, corroles, cancer, diabetes, neurodegenerative diseases, metallocorroles, cell-internalizing motifs, of penicillin/streptomycin/nystatin, Minimum Essential Medium, paraformaldehyde solution, cholesterol biosynthesis, b cells (insulinoma)