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  • Deiana, MarcoUmeå universitet,Institutionen för medicinsk kemi och biofysik (author)

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

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • Oxford University Press,2023
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-212227
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-212227URI
  • https://doi.org/10.1093/nar/gkad365DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Photodynamic 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.

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  • Andrés Castán, José MaríaUniv Angers, CNRS, MOLTECH-ANJOU, France (author)
  • Josse, PierreUniv Angers, CNRS, MOLTECH-ANJOU, France (author)
  • Kahsay, AbrahaUmeå universitet,Institutionen för integrativ medicinsk biologi (IMB)(Swepub:umu)abge0003 (author)
  • Sánchez, Darío PuchánUniv Angers, CNRS, MOLTECH-ANJOU, France (author)
  • Morice, KorentinUniv Angers, CNRS, MOLTECH-ANJOU, France (author)
  • Gillet, NatachaENS de Lyon, CNRS, Laboratoire de Chimie UMR 5182, Université Claude Bernard Lyon 1, France (author)
  • Ravindranath, RanjithaENS de Lyon, CNRS, Laboratoire de Chimie UMR 5182, Université Claude Bernard Lyon 1, France; Indian Institute for Science Education and Research (IISER), Tirupati, India (author)
  • Patel, Ankit KumarUmeå universitet,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Onkologi(Swepub:umu)anku0073 (author)
  • Sengupta, PallabiUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)pase0028 (author)
  • Obi, IkennaUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)ikob0001 (author)
  • Rodriguez-Marquez, EvaUmeå universitet,Institutionen för integrativ medicinsk biologi (IMB)(Swepub:umu)evro0021 (author)
  • Khrouz, LhoussainENS de Lyon, CNRS, Laboratoire de Chimie UMR 5182, Université Claude Bernard Lyon 1, France (author)
  • Dumont, EliseENS de Lyon, CNRS, Laboratoire de Chimie UMR 5182, Université Claude Bernard Lyon 1, France; Institut Universitaire de France, 5 rue Descartes, France (author)
  • Abad Galán, LauraENS de Lyon, CNRS, Laboratoire de Chimie UMR 5182, Université Claude Bernard Lyon 1, France (author)
  • Allain, MagaliUniv Angers, CNRS, MOLTECH-ANJOU, France (author)
  • Walker, BrightDepartment of Chemistry, Kyung Hee University, Seoul, South Korea (author)
  • Ahn, Hyun SeoYonsei University, 50 Yonsei-ro ,Seodaemun-gu, Seoul, South Korea (author)
  • Maury, OlivierENS de Lyon, CNRS, Laboratoire de Chimie UMR 5182, Université Claude Bernard Lyon 1, France (author)
  • Blanchard, PhilippeUniv Angers, CNRS, MOLTECH-ANJOU, France (author)
  • Le Bahers, TanguiENS de Lyon, CNRS, Laboratoire de Chimie UMR 5182, Université Claude Bernard Lyon 1, France; Institut Universitaire de France, 5 rue Descartes, France (author)
  • Öhlund, Daniel,1979-Umeå universitet,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Onkologi(Swepub:umu)dalohd00 (author)
  • von Hofsten, JonasUmeå universitet,Institutionen för integrativ medicinsk biologi (IMB)(Swepub:umu)josvon97 (author)
  • Monnereau, CyrilleENS de Lyon, CNRS, Laboratoire de Chimie UMR 5182, Université Claude Bernard Lyon 1, France (author)
  • Cabanetos, ClémentUniv Angers, CNRS, MOLTECH-ANJOU, France; Yonsei University, 50 Yonsei-ro ,Seodaemun-gu, Seoul, South Korea; Yonsei University, Building Blocks for FUture Electronics Laboratory (2BFUEL), Seoul, South Korea (author)
  • Sabouri, NasimUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)namsai01 (author)
  • Umeå universitetInstitutionen för medicinsk kemi och biofysik (creator_code:org_t)

Related titles

  • In:Nucleic Acids Research: Oxford University Press51:12, s. 6264-62850305-10481362-4962

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