Staff member


Alexandre Gomila Juaneda

PhD Student
Nanoprobes and Nanoswitches
agomila@ibecbarcelona.eu
+34 93 403 76 47
Staff member publications

Riefolo, F., Matera, C., Garrido-Charles, A., Gomila, A., Sortino, R., Agnetta, L., Claro, E., Masgrau, R., Holzgrabe, U., Batlle, M., Decker, M., Guasch, E., Gorostiza, P., (2019). Optical control of cardiac function with a photoswitchable muscarinic agonist Journal of the American Chemical Society 141, (18), 7628-7636

Light-triggered reversible modulation of physiological functions offers the promise of enabling on-demand spatiotemporally controlled therapeutic interventions. Optogenetics has been successfully implemented in the heart, but significant barriers to its use in the clinic remain, such as the need for genetic transfection. Herein, we present a method to modulate cardiac function with light through a photoswitchable compound and without genetic manipulation. The molecule, named PAI, was designed by introduction of a photoswitch into the molecular structure of an M2 mAChR agonist. In vitro assays revealed that PAI enables light-dependent activation of M2 mAChRs. To validate the method, we show that PAI photoisomers display different cardiac effects in a mammalian animal model, and demonstrate reversible, real-time photocontrol of cardiac function in translucent wildtype tadpoles. PAI can also effectively activate M2 receptors using two-photon excitation with near-infrared light, which overcomes the scattering and low penetration of short-wave-length illumination, and offers new opportunities for intravital imaging and control of cardiac function.


Matera, C., Gomila, A. M. J., Camarero, N., Libergoli, M., Soler, C., Gorostiza, P., (2019). Photochromic antifolate for light-activated chemotherapy Proceedings of SPIE 17th International Photodynamic Association World Congress , SPIE (Cambridge, USA) 11070, 110709H

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.

Keywords: Cancer, Dermatology, Methotrexate, Photoactivated chemotherapy, Photodynamic therapy, Phototherapy, Psoriasis, Rheumatoid arthritis