| 1. |
- Deiana, Marco, et al.
(författare)
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A new G-quadruplex-specific photosensitizer inducing genome instability in cancer cells by triggering oxidative DNA damage and impeding replication fork progression
- 2023
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Ingår i: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 51:12, s. 6264-6285
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Deiana, Marco, et al.
(författare)
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Light-induced in situ chemical activation of a fluorescent probe for monitoring intracellular G-quadruplex structures
- 2021
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Ingår i: Nanoscale. - : Royal Society of Chemistry. - 2040-3364 .- 2040-3372. ; 13:32, s. 13795-13808
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Tidskriftsartikel (refereegranskat)abstract
- Light-activated functional materials capable of remote control over duplex and G-quadruplex (G4) nucleic acids formation at the cellular level are still very rare. Herein, we report on the photoinduced macrocyclisation of a helicenoid quinoline derivative of binaphthol that selectively provides easy access to an unprecedented class of extended heteroaromatic structures with remarkable photophysical and DNA/RNA binding properties. Thus, while the native bisquinoline precursor shows no DNA binding activity, the new in situ photochemically generated probe features high association constants to DNA and RNA G4s. The latter inhibits DNA synthesis by selectively stabilizing G4 structures associated with oncogenic promoters and telomere repeat units. Finally, the light sensitive compound is capable of in cellulo photoconversion, localizes primarily in the G4-rich sites of cancer cells, competes with a well-known G4 binder and shows a clear nuclear co-localization with the quadruplex specific antibody BG4. This work provides a benchmark for the future design and development of a brand-new generation of light-activated target-selective G4-binders.
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| 3. |
- Deiana, Marco, et al.
(författare)
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Site-selected thionated benzothioxanthene chromophores as heavy-atom-free small-molecule photosensitizers for photodynamic therapy
- 2022
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Ingår i: Communications Chemistry. - : Springer Nature. - 2399-3669. ; 5
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Tidskriftsartikel (refereegranskat)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.
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| 4. |
- Norrbo, Isabella, et al.
(författare)
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Solar UV index and UV dose determination with photochromic hackmanites : from the assessment of the fundamental properties to the device
- 2018
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Ingår i: Materials Horizons. - : Royal Society of Chemistry (RSC). - 2051-6347 .- 2051-6355. ; 5:3, s. 569-576
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Tidskriftsartikel (refereegranskat)abstract
- Extended exposure to sunlight or artificial UV sources is a major cause of serious skin and eye diseases such as cancer. There is thus a great need for convenient materials for the easy monitoring of UV doses. While organic photochromic molecules are tunable for responses under different wavelengths of UV radiation, they suffer from rather poor durability because the color changes involve drastic changes in molecular structure. Inorganic materials, on the other hand, are durable, but they have lacked tunability. Here, by combining computational and empirical data, we confirm the mechanism of coloration in the hackmanites, nature-based materials, and introduce a new technique called thermotenebrescence. With knowledge of the mechanism, we show that we can control and thus tune the energy of electronic states of synthetic hackmanites (Na,M)(8)Al6Si6O24(Cl,S)(2) so that their body color is sensitive to the solar UV index as well as UVA, UVB or UVC radiation levels. Finally, we demonstrate that it is possible to use images taken with an inexpensive cell phone to quantify the radiation dose or UV index. The hackmanite materials thus show great potential for use in portable healthcare both in everyday life and in laboratories.
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