Towards Selective Delivery of a Ruthenium(II) Polypyridyl Complex-Containing Bombesin Conjugate into Cancer Cells |
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| Authors: | Dr Maria J S A Silva Dr Robin Vinck Youchao Wang Dr Bruno Saubaméa Dr Mickaël Tharaud Elena Dominguez-Jurado Dr Johannes Karges Prof?Dr Pedro M P Gois Prof?Dr Gilles Gasser |
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| Affiliation: | 1. Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal;2. Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, 75005 Paris, France;3. Cellular and Molecular Imaging Facility, US25 Inserm, UAR3612 CNRS, Faculté de Pharmacie de Paris, Université Paris Cité, 75006 Paris, France;4. Université Paris Cité, Institut de Physique du Globe de Paris, CNRS, 75005 Paris, France;5. Faculty of Pharmacy of Albacete, Universidad de Castilla–La Mancha, 02008 Albacete, Spain |
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| Abstract: | An increasing number of novel Ru(II) polypyridyl complexes have been successfully applied as photosensitizers (PSs) for photodynamic therapy (PDT). Despite recent advances in optimized PSs with refined photophysical properties, the lack of tumoral selectivity is often a major hurdle for their clinical development. Here, classical maleimide and versatile NHS-activated acrylamide strategies were employed to site-selectively conjugate a promising Ru(II) polypyridyl complex to the N-terminally Cys-modified Bombesin (BBN) targeting unit. Surprisingly, the decreased cell uptake of these novel Ru-BBN conjugates in cancer cells did not hamper the high phototoxic activity of the Ru-containing bioconjugates and even decreased the toxicity of the constructs in the absence of light irradiation. Overall, although deceiving in terms of selectivity, our new bioconjugates could still be useful for advanced cancer treatment due to their nontoxicity in the dark. |
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| Keywords: | bombesin medicinal inorganic chemistry metals in medicine photodynamic therapy ruthenium |
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