A near-infrared light-activatable Ru(ii)-coumarin photosensitizer active under hypoxic conditions

Enrique Ortega-Forte, Anna Rovira, Marta López-Corrales, Alba Hernández-García, Francisco José Ballester, Eduardo Izquierdo-García, Mireia Jordà-Redondo, Manel Bosch, Santi Nonell, María Dolores Santana, José Ruiz, Vicente Marchán, Gilles Gasser

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12 Cites (Scopus)


Photodynamic therapy (PDT) represents a promising approach for cancer treatment. However, the oxygen dependency of PDT to generate reactive oxygen species (ROS) hampers its therapeutic efficacy, especially against hypoxic solid tumors. In addition, some photosensitizers (PSs) have dark toxicity and are only activatable with short wavelengths such as blue or UV-light, which suffer from poor tissue penetration. Herein, we developed a novel hypoxia-active PS with operability in the near-infrared (NIR) region based on the conjugation of a cyclometalated Ru(ii) polypyridyl complex of the type [Ru(C<^>N)(N<^>N)(2)] to a NIR-emitting COUPY dye. The novel Ru(ii)-coumarin conjugate exhibits water-solubility, dark stability in biological media and high photostability along with advantageous luminescent properties that facilitate both bioimaging and phototherapy. Spectroscopic and photobiological studies revealed that this conjugate efficiently generates singlet oxygen and superoxide radical anions, thereby achieving high photoactivity toward cancer cells upon highly-penetrating 740 nm light irradiation even under hypoxic environments (2% O-2). The induction of ROS-mediated cancer cell death upon low-energy wavelength irradiation along with the low dark toxicity exerted by this Ru(ii)-coumarin conjugate could circumvent tissue penetration issues while alleviating the hypoxia limitation of PDT. As such, this strategy could pave the way to the development of novel NIR- and hypoxia-active Ru(ii)-based theragnostic PSs fuelled by the conjugation of tunable, low molecular-weight COUPY fluorophores.
Idioma originalAnglès
Número d’articled3sc01844j
Pàgines (de-a)7170-7184
Nombre de pàgines15
RevistaChemical Science
Estat de la publicacióPublicada - 8 de juny 2023


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