TY - JOUR
T1 - A near-infrared light-activatable Ru(ii)-coumarin photosensitizer active under hypoxic conditions
AU - Ortega-Forte, Enrique
AU - Rovira, Anna
AU - López-Corrales, Marta
AU - Hernández-García, Alba
AU - Ballester, Francisco José
AU - Izquierdo-García, Eduardo
AU - Jordà-Redondo, Mireia
AU - Bosch, Manel
AU - Nonell, Santi
AU - Santana, María Dolores
AU - Ruiz, José
AU - Marchán, Vicente
AU - Gasser, Gilles
N1 - Funding Information:
This work was supported by funds from the Spanish Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación (MCI/AEI/10.13039/501100011033) and FEDER funds (Projects PID2020-117508RB-I00, PID2021-122850NB-I00 and PID2020-115801RB-C22). The stay of E. O.-F. in G. G. laboratory was funded by a scholarship from EIDUM-CMN of University of Murcia. This work was financially supported by an ERC Consolidator Grant Photo-MedMet to G. G. (GA 681679) and has received support under the program ‘‘Investissements d’Avenir’’ launched by the French Government and implemented by the ANR with the reference ANR-10-IDEX-0001-02 PSL (G. G.). E. O.-F thanks AECC (Project PRDMU19003ORTE). A. R. and M. L.-C. were recipient fellows of the University of Barcelona (APIF) and of the Generalitat de Catalunya (FI-SDUR), respectively. E. I.-G. acknowledges support from a Margarita Salas University of Barcelona postdoctoral grant funded by the Spanish Ministerio de Universidades with European Union funds – NextGenerationEU. The authors acknowledge helpful assistance from Dr Francisco Cárdenas (NMR) and Dr Irene Fernández and Laura Ortiz (MS) from CCiTUB.
Funding Information:
This work was supported by funds from the Spanish Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación (MCI/AEI/10.13039/501100011033) and FEDER funds (Projects PID2020-117508RB-I00, PID2021-122850NB-I00 and PID2020-115801RB-C22). The stay of E. O.-F. in G. G. laboratory was funded by a scholarship from EIDUM-CMN of University of Murcia. This work was financially supported by an ERC Consolidator Grant Photo-MedMet to G. G. (GA 681679) and has received support under the program ‘‘Investissements d’Avenir’’ launched by the French Government and implemented by the ANR with the reference ANR-10-IDEX-0001-02 PSL (G. G.). E. O.-F thanks AECC (Project PRDMU19003ORTE). A. R. and M. L.-C. were recipient fellows of the University of Barcelona (APIF) and of the Generalitat de Catalunya (FI-SDUR), respectively. E. I.-G. acknowledges support from a Margarita Salas University of Barcelona postdoctoral grant funded by the Spanish Ministerio de Universidades with European Union funds - NextGenerationEU. The authors acknowledge helpful assistance from Dr Francisco Cárdenas (NMR) and Dr Irene Fernández and Laura Ortiz (MS) from CCiTUB.
Publisher Copyright:
© 2023 The Royal Society of Chemistry.
PY - 2023/6/8
Y1 - 2023/6/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85163593423&partnerID=8YFLogxK
U2 - 10.1039/d3sc01844j
DO - 10.1039/d3sc01844j
M3 - Article
AN - SCOPUS:85163593423
SN - 2041-6520
VL - 14
SP - 7170
EP - 7184
JO - Chemical Science
JF - Chemical Science
IS - 26
M1 - d3sc01844j
ER -
