A Molecular Hybrid for Mitochondria‐Targeted NO Photodelivery |
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Authors: | Dr. Federica Sodano Dr. Elena Gazzano Dr. Aurore Fraix Prof. Barbara Rolando Dr. Loretta Lazzarato Dr. Marina Russo Dr. Marco Blangetti Prof. Chiara Riganti Prof. Roberta Fruttero Prof. Alberto Gasco Prof. Salvatore Sortino |
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Affiliation: | 1. Department of Science and Drug Technology, University of Torino, Torino, Italy;2. Department of Oncology, University of Torino, Torino, Italy;3. Laboratory of Photochemistry, Department of Drug Sciences, University of Catania, Catania, Italy |
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Abstract: | The design, synthesis, spectroscopic and photochemical properties, and biological evaluation of a novel molecular hybrid that is able to deliver nitric oxide (NO) into mitochondria are reported. This molecular conjugate unites a tailored o‐CF3‐p‐nitroaniline chromophore, for photo‐regulated NO release, and a rhodamine moiety, for mitochondria targeting, in the same molecular skeleton via an alkyl spacer. A combination of steady‐state and time‐resolved spectroscopic and photochemical experiments demonstrate that the two chromogenic units preserve their individual photophysical and photochemical properties in the conjugate quite well. Irradiation with violet light triggers NO release from the nitroaniline moiety and photoionization in the rhodamine center, which also retains considerable fluorescence efficiency. The molecular hybrid preferentially accumulates in the mitochondria of A549 lung adenocarcinoma cells where it induces toxicity at a concentration of 1 μm , exclusively upon irradiation. Comparative experiments, carried out with ad‐hoc‐synthesized model compounds, suggest that the phototoxicity observed at such a low concentration is probably not due to NO itself, but rather to the formation of the highly reactive peroxynitrite that is generated from the reaction of NO with the superoxide anion. |
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Keywords: | light nitric oxide rhodamine targeted therapy |
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