RT Journal Article
T1 A new G-quadruplex-specific photosensitizer inducing genome instability in cancer cells by triggering oxidative DNA damage and impeding replication fork progression
A1 Deiana, Marco
A1 Andrés Castán, José María
A1 Josse, Pierre
A1 Kahsay, Abraha
A1 Puchán Sánchez, Darío
A1 Morice, Korentin
A1 Gillet, Natacha
A1 Ravindranath, Ranjitha
A1 Kumar Patel, Ankit
A1 Sengupta, Pallabi
A1 Obi, Ikenna
A1 Rodriguez-Marquez, Eva
A1 Khrouz, Lhoussain
A1 Dumont, Elise
A1 Abad Galán, Laura
A1 Allain, Magali
A1 Walker, Bright
A1 Seo Ahn, Hyun
A1 Maury, Olivier
A1 Blanchard, Philippe
A1 Le Bahers, Tangui
A1 Öhlund, Daniel
A1 Hofsten, Jonas von
A1 Monnereau, Cyrille
A1 Cabanetos, Clément
A1 Sabouri, Nasim
AB AbstractPhotodynamic therapy (PDT) ideally relies on the administration, selective accumulation and photoactivation of a photosensitizer (PS) into diseased tissues. In this context, we report a new heavy-atom-free fluorescent G-quadruplex (G4) DNA-binding PS, named DBI. We reveal by fluorescence microscopy that DBI preferentially localizes in intraluminal vesicles (ILVs), precursors of exosomes, which are key components of cancer cell proliferation. Moreover, purified exosomal DNA was recognized by a G4-specific antibody, thus highlighting the presence of such G4-forming sequences in the vesicles. Despite the absence of fluorescence signal from DBI in nuclei, light-irradiated DBI-treated cells generated reactive oxygen species (ROS), triggering a 3-fold increase of nuclear G4 foci, slowing fork progression and elevated levels of both DNA base damage, 8-oxoguanine, and double-stranded DNA breaks. Consequently, DBI was found to exert significant phototoxic effects (at nanomolar scale) toward cancer cell lines and tumor organoids. Furthermore, in vivo testing reveals that photoactivation of DBI induces not only G4 formation and DNA damage but also apoptosis in zebrafish, specifically in the area where DBI had accumulated. Collectively, this approach shows significant promise for image-guided PDT.
PB Oxford University Press
SN 0305-1048
YR 2023
FD 2023
LK https://hdl.handle.net/20.500.14352/92127
UL https://hdl.handle.net/20.500.14352/92127
LA eng
NO Deiana, M.; Andrés Castán, J.; Josse, P.; Kahsay, A.; Sánchez, D. P.; Morice, K.; Gillet, N.; Ravindranath, R.; Patel, A. K.; Sengupta, P.; Obi, I.; Rodriguez-Marquez, E.; Khrouz, L.; Dumont, E.; Abad Galán, L.; Allain, M.; Walker, B.; Ahn, H. S.; Maury, O.; Blanchard, P.; Le Bahers, T.; Öhlund, D.; von Hofsten, J.; Monnereau, C.; Cabanetos, C.; Sabouri, N. A new G-quadruplex-specific photosensitizer inducing genome instability in cancer cells by triggering oxidative DNA damage and impeding replication fork progression. Nucleic Acids Res. 2023, 51, 6264-6285 DOI:10.1093/nar/gkad365.
DS Docta Complutense
RD 9 abr 2025