Prof. Concepció Soler Profile

Prof. Concepció Soler

at Univ. de Barcelona

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Proceedings Article | 7 August 2019

Photochromic antifolate for light-activated chemotherapy

Carlo Matera, Alexandre M. Gomila, Núria Camarero, Michela Libergoli, Concepció Soler, Pau Gorostiza

Proc. SPIE. 11070, 17th International Photodynamic Association World Congress

KEYWORDS: Switches, Phototherapy, Oncology, Photodynamic therapy, Cancer, Dermatology, Skin, Medical research, Toxicity, Absorption

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Although cytotoxic chemotherapy is one of the primary pharmacological treatments for chronic hyperproliferative diseases such as cancer and psoriasis, its efficacy and tolerability are in many cases dramatically limited by off-target toxicity. A promising approach to improve these therapies is to activate the drugs exclusively at their desired place of action. In fact, in those diseases that would benefit from a highly localized treatment, a precise spatiotemporal control over the activity of a chemotherapeutic agent would allow reducing the concentration of active compound outside the targeted region, improving the tolerability of the treatment. Light is a powerful tool in this respect: it offers unparalleled opportunities as a non-invasive regulatory signal for pharmacological applications because it can be delivered with high precision regarding space, time, intensity and wavelength. Photopharmacology represents a new and emerging approach in this regard since the energy of light is used to change the structure of the drug and hence to switch its pharmacological activity on and off on demand. We describe here phototrexate, the first light-regulated inhibitor of the human DHFR. Enzyme and cell viability assays demonstrated that phototrexate behaves as a potent antifolate in its cis configuration, obtained under UVA illumination, and that it is nearly inactive in its dark-relaxed trans form. Experiments in zebrafish confirmed that phototrexate can disrupt folate metabolism in a light-dependent fashion also in vivo. Overall, phototrexate represents a potential candidate towards the development of an innovative photoactivated antifolate chemotherapy.

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