@article{Deiana2023,

title = {A new G-quadruplex-specific photosensitizer inducing genome instability in cancer cells by triggering oxidative DNA damage and impeding replication fork progression},

author = {Marco Deiana and José María Andrés Castán and Pierre Josse and Abraha Kahsay and Darío Puchán Sánchez and Korentin Morice and Natacha Gillet and Ranjitha Ravindranath and Ankit Kumar Patel and Pallabi Sengupta and Ikenna Obi and Eva Rodriguez-Marquez and Lhoussain Khrouz and Elise Dumont and Laura Abad Galán and Magali Allain and Bright Walker and Hyun Seo Ahn and Olivier Maury and Philippe Blanchard and Tangui Le Bahers and Daniel Öhlund and Jonas von Hofsten and Cyrille Monnereau and Clément Cabanetos and Nasim Sabouri},

doi = {10.1093/nar/gkad365},

issn = {1362-4962},

year  = {2023},

date = {2023-07-07},

volume = {51},

number = {12},

pages = {6264--6285},

publisher = {Oxford University Press (OUP)},

abstract = {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.},

keywords = {Genetics},

pubstate = {published},

tppubtype = {article}

}