ORCID Profile
0000-0002-7815-4494
Current Organisation
Wrocław University of Science and Technology
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Publisher: Oxford University Press (OUP)
Date: 16-05-2023
DOI: 10.1093/NAR/GKAD365
Abstract: 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.
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2NR90225G
Abstract: Correction for ‘Light-induced in situ chemical activation of a fluorescent probe for monitoring intracellular G-quadruplex structures’ by Marco Deiana et al. , Nanoscale , 2021, 13 , 13795–13808, 0.1039/D1NR02855C.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1NR02855C
Abstract: A photochemically generated fluorophore is used to monitor intracellular G-quadruplex structures.
Publisher: Springer Science and Business Media LLC
Date: 31-10-2022
DOI: 10.1038/S42004-022-00752-X
Abstract: Photodynamic therapy is a clinically approved anticancer modality that employs a light-activated agent (photosensitizer) to generate cytotoxic reactive oxygen species (ROS). There is therefore a growing interest for developing innovative photosensitizing agents with enhanced phototherapeutic performances. Herein, we report on a rational design synthetic procedure that converts the ultrabright benzothioxanthene imide ( BTI ) dye into three heavy-atom-free thionated compounds featuring close-to-unit singlet oxygen quantum yields. In contrast to the BTI , these thionated analogs display an almost fully quenched fluorescence emission, in agreement with the formation of highly populated triplet states. Indeed, the sequential thionation on the BTI scaffold induces torsion of its skeleton reducing the singlet-triplet energy gaps and enhancing the spin-orbit coupling. These potential PSs show potent cancer-cell ablation under light irradiation while remaining non-toxic under dark condition owing to a photo-cytotoxic mechanism that we believe simultaneously involves singlet oxygen and superoxide species, which could be both characterized in vitro. Our study demonstrates that this simple site-selected thionated platform is an effective strategy to convert conventional carbonyl-containing fluorophores into phototherapeutic agents for anticancer PDT.
No related grants have been discovered for Marco Deiana.