Metallation of pentaphyrin with Lu(III) dramatically increases reactive-oxygen species production and cell phototoxicity

Photodynamic therapy (PDT) is an emerging cancer treatment modality based on the excitation of a nontoxic photosensitizer with harmless visible light to produce reactive-oxygen species (ROS) that induce apoptosis and/or necrosis in cancer cells. As the efficacy of this therapy strongly depends of the nature of the photosensitizer, there is a great interest to develop new photoactive molecules. Here we report for the first time the synthesis, characterization and bioactivity of metal complexes between the non-aromatic expanded porphyrin, namely 20-[[4′-(Trimethylsilyl)ethoxycarbonyl]phenyl-2,13-dimethyl-3,12-diethyl-[24] iso-pentaphyrin (PCRed) and Zn(II) [Zn(II)–PCRed] or Lu(III) [Lu(III)–PCRed]. The complexation of these two diamagnetic heavy metal ions to PCRed improved the properties of the free photosensitizer as a PDT drug. We discovered that the 1:1 complex between PCRed and Lu(III) significantly increases the cellular uptake, ROS production and antiproliferative capacity in four cancer cell lines. Our study shows that metal complexation is a useful strategy to potentiate iso-pentaphyrin as a PDT drug.

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► Synthesis and characterization of [1.1.1.1.1] iso-pentaphyrin and its Zn(II) and Lu(III) complexes.
► Phototoxicity of [1.1.1.1.1] iso-pentaphyrin and relative Zn(II) and Lu(III) complexes in cancer cell lines.
► Heavy metal effect upon coordination of Lu(III) to pentaphyrin.
► Increase of ROS production upon coordination of Lu(III) to pentaphyrin.