| 1. |
- Deiana, Marco, et al.
(author)
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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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In: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 51:12, s. 6264-6285
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Journal article (peer-reviewed)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.
(author)
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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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In: Nanoscale. - : Royal Society of Chemistry. - 2040-3364 .- 2040-3372. ; 13:32, s. 13795-13808
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Journal article (peer-reviewed)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.
(author)
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Site-selected thionated benzothioxanthene chromophores as heavy-atom-free small-molecule photosensitizers for photodynamic therapy
- 2022
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In: Communications Chemistry. - : Springer Nature. - 2399-3669. ; 5
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Journal article (peer-reviewed)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. |
- Göransson, Erik, et al.
(author)
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Photoinduced Electron Transfer in Zn(II)porphyrin-Bridge-Pt(II)acetylide Complexes : Variation in Rate with Anchoring Group and Position of the Bridge
- 2010
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In: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 49:21, s. 9823-9832
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Journal article (peer-reviewed)abstract
- The synthesis and photophysical characterization of two sets of zinc porphyrin platinum acetylide complexes are reported. The two sets of molecules differ in the way the bridging phenyl-ethynyl unit is attached to the porphyrin ring. One set is attached via an ethynyl unit on the beta position, while the other set is attached via a phenyl unit on the meso position of the porphyrin. These were compared with previously studied complexes where attachment was made via an ethynyl unit on the meso position. Femtosecond transient absorption measurements showed in all systems a rapid quenching of the porphyrin singlet state. Electron transfer is suggested as the quenching mechanism, followed by an even faster recombination to form both the porphyrin ground and triplet excited states. This is supported by the variation in quenching rate and porphyrin triplet yield with solvent polarity, and the observation of an intermediate state in the meso-phenyl linked systems. The different linking motifs between the dyads resulted in significant variations in electron transfer rates.
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| 5. |
- Lerouge, Frederic, et al.
(author)
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In vivo targeting and multimodal imaging of cerebral amyloid-beta aggregates using hybrid GdF3 nanoparticles
- 2022
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In: Nanomedicine. - : FUTURE MEDICINE LTD. - 1743-5889 .- 1748-6963. ; 17:29, s. 2173-2187
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Journal article (peer-reviewed)abstract
- Aim: To propose a new multimodal imaging agent targeting amyloid-beta (A beta) plaques in Alzheimers disease. Materials & methods: A new generation of hybrid contrast agents, based on gadolinium fluoride nanoparticles grafted with a pentameric luminescent-conjugated polythiophene, was designed, extensively characterized and evaluated in animal models of Alzheimers disease through MRI, two-photon microscopy and synchrotron x-ray phase-contrast imaging. Results & conclusion: Two different grafting densities of luminescent-conjugated polythiophene were achieved while preserving colloidal stability and fluorescent properties, and without affecting biodistribution. In vivo brain uptake was dependent on the blood-brain barrier status. Nevertheless, multimodal imaging showed successful A beta targeting in both transgenic mice and A beta fibril-injected rats.
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| 6. |
- Lunden, Hampus, et al.
(author)
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An optical power limiting and ultrafast photophysics investigation of a series of multi-branched heavy atom substituted fluorene molecules
- 2019
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In: Inorganics. - : MDPI AG. - 2304-6740. ; 7:10
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Journal article (peer-reviewed)abstract
- A common molecular design paradigm for optical power limiting (OPL) applications is to introduce heavy atoms that promote intersystem crossing and triplet excited states. In order to investigate this effect, three multi-branched fluorene molecules were prepared where the central moiety was either an organic benzene unit, para-dibromobenzene, or a platinum(II)-alkynyl unit. All three molecules showed good nanosecond OPL performance in solution. However, only the dibromobenzene and Pt-alkynyl compounds showed strong microsecond triplet excited state absorption (ESA). To investigate the photophysical cause of the OPL, especially for the fully organic molecule, photokinetic measurements including ultrafast pump-probe spectroscopy were performed. At nanosecond timescales, the ESA of the organic molecule was larger than the two with intersystem crossing (ISC) promoters, explaining its good OPL performance. This points to a design strategy where the singlet-state ESA is balanced with the ISC rate to increase OPL performance at the beginning of a nanosecond pulse.
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| 7. |
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| 8. |
- Rouillon, Jean, 1993, et al.
(author)
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Assembly of Aggregation-Induced Emission Active Bola-Amphiphilic Macromolecules into Luminescent Nanoparticles Optimized for Two-Photon Microscopy In Vivo
- 2022
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In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 23:6, s. 2485-2495
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Journal article (peer-reviewed)abstract
- The (Z) and (E)-isomers of an extended tetraphenylethylene-based chromophore with optimized two-photon-induced luminescence properties are separated and functionalized with water-solubilizing pendant polymer groups, promoting their self-assembly in physiological media in the form of small, colloidal stable organic nanoparticles. The two resulting fluorescent suspensions are then evaluated as potential two-photon luminescent contrast agents for intravital epifluorescence and two-photon fluorescence microscopy. Comparisons with previously reported works involving similar fluorophores devoid of polymer side chains illustrate the benefits of later functionalization regarding the control of the self-assembly of the nano-objects and ultimately their biocompatibility toward the imaged organism.
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| 9. |
- Sánchez, Darío Puchán, et al.
(author)
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Heavy-atom-free π-twisted photosensitizers for fluorescence bioimaging and photodynamic therapy
- 2024
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In: Journal of materials chemistry. B. - : Royal Society of Chemistry. - 2050-750X .- 2050-7518.
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Journal article (peer-reviewed)abstract
- As the field of preclinical research on photosensitizers (PSs) for anticancer photodynamic therapy (PDT) continues to expand, a focused effort is underway to develop agents with innovative molecular structures that offer enhanced targeting, selectivity, activation, and imaging capabilities. In this context, we introduce two new heavy-atom-free PSs, DBXI and DBAI, characterized by a twisted π-conjugation framework. This innovative approach enhances the spin-orbit coupling (SOC) between the singlet excited state (S1) and the triplet state (T1), resulting in improved and efficient intersystem crossing (ISC). Both PSs are highly effective in producing reactive oxygen species (ROS), including singlet oxygen and/or superoxide species. Additionally, they also demonstrate remarkably strong fluorescence emission. Indeed, in addition to providing exceptional photocytotoxicity, this emissive feature, generally lacking in other reported structures, allows for the precise monitoring of the PSs’ distribution within specific cellular organelles even at nanomolar concentrations. These findings underscore the dual functionality of these PSs, serving as both fluorescent imaging probes and light-activated therapeutic agents, emphasizing their potential as versatile and multifunctional tools in the field of PDT.
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| 10. |
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