Photo-induced telomeric DNA damage in human cancer cells

Weynand, Justin; Episkopou, Harikleia; Berre, Gabriel Le; Gillard, Martin; Dejeu, Jérôme; Decottignies, Anabelle; Defrancq, Éric; Elias, Benjamin

doi:10.1039/d2cb00192f

Cited by 7 publications

(5 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, PDT can induce hypoxia as oxygen is consumed during irradiation. , Decreased generation of ROS limits damage to cancerous cells. To address this, there is motivation to develop light-triggered compounds that exploit oxygen-independent mechanisms for phototoxicity. − In this context, metal complexes such as Ru(II) polypyridyl systems have attracted considerable attention. ,,,− Judicious choice of ligand–metal combinations provides access to a variety of excited-state configurations with characteristic photophysical properties and reactivities. Strategies have included photorelease of bulky ligands to reveal phototoxic metals and/or ligands, ,,,,,− photocaging of chemotherapeutics and enzyme inhibitors, ,,,,,− …”

Section: Introductionmentioning

confidence: 99%

Ru(II) Phenanthroline-Based Oligothienyl Complexes as Phototherapy Agents

Cole,

Vali,

Roque

et al. 2023

Inorg. Chem.

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Ru(II) Phenanthroline-Based Oligothienyl Complexes as Phototherapy Agents

Cole,

Vali,

Roque

et al. 2023

Inorg. Chem.

View full text Add to dashboard Cite

“…Indeed, one of the most compelling ways to confirm the G4 presence in vivo is by direct visualization, e.g., through fluorescence imaging. The earliest imaging-based evidence for in cellulo G4 originated from fixed cell studies using labeled antibodies toward G4. , G4s have been recently visualized in live cells using fluorescence lifetime imaging (FLIM). , Inorganic probes are an attractive option for in cellulo detection of G4s as a number of luminescent coordination compounds are well-established probes of DNA and have been characterized in detail in this regard. − Complexes of Ru(II) and Ir(III) have been widely studied as DNA binders with the capacity to report on the structure and also to induce photodamage both in solution and more recently in cellulo. − From the imaging perspective, Ru(II) and Os(II) complexes maintain a number of photophysical benefits over organic alternatives including their large Stokes shifts, environmentally sensitive emission, and long-lived phosphorescent lifetimes; combined, these properties make such probes suitable for mutimodal imaging, making them an exciting prospect to explore G4 visualization in live cells. − …”

Section: Introductionmentioning

confidence: 99%

Selective, Disruptive Luminescent Ru(II) Polypyridyl Probes of G-Quadruplex

et al. 2023

View full text Add to dashboard Cite

Sensors capable of transducing G-quadruplex DNA binding are important both in solution and for imaging and interrogation in cellulo. Ru(II)-based light switches incorporating dipyridylphenazine (dppz) ligands are effective probes for recognition and imaging of DNA and its polymorphs including G-quadruplex, although selectivity is a limitation. While the majority of Ru(II)-based light switches reported to date, stabilize the quadruplex, imaging/theranostic probes that can disrupt G4s are of potentially enormous value in study and therapy for a range of disease states. We report here, on a Ru(II) complex (Ru-PDC3) that assembles the light switch capability of a Ru(II) dipyridylphenazine complex with the well-known G4-selective ligand Phen-DC3, into a single structure. The complex shows the anticipated light switch effect and strong affinity for G4 structures. Affinity depended on the G4 topology and sequence, but across all structures bar one, it was roughly an order of magnitude greater than for duplex or single-stranded DNA. Moreover, photophysical and Raman spectral data showed clear discrimination between duplex DNA and G4-bound structures offering the prospect of discrimination in imaging as well as in solution. Crucially, unlike the constituent components of the probe, Ru-PDC3 is a powerful G4 disrupter. From circular dichroism (CD), a reduction of ellipticity of the G4 between 70 and 95% was observed depending on topology and in many cases was accompanied by an induced CD signal for the metal complex. The extent of change in ellipticity is amongst the largest reported for small-molecule ligand G4 binding. While a promising G4 probe, without modification, the complex is fully water-soluble and readily permeable to live cells.

show abstract

“…Thus, there has been increasing attention on the synthesis of ligands that can selectively target multimeric G4s. , Such DNA binders can generally be grouped into two categories: those where a single binder is “sandwiched” between two G4 units, − and those containing two linked G4 binders that interact with two different tetrads − (Figure b). Recent work by our group showed that a dimeric metal complex could selectively stabilize dimeric over monomeric G4 DNA .…”

Section: Introductionmentioning

confidence: 99%

Dimeric Metal-Salphen Complexes Which Target Multimeric G-Quadruplex DNA

et al. 2023

View full text Add to dashboard Cite

G-Quadruplex DNA structures have attracted increasing attention due to their biological roles and potential as targets for the development of new drugs. While most guanine-rich sequences in the genome have the potential to form monomeric G-quadruplexes, certain sequences have enough guanine-tracks to give rise to multimeric quadruplexes. One of these sequences is the human telomere where tandem repeats of TTAGGG can lead to the formation of two or more adjacent G-quadruplexes. Herein we report on the modular synthesis via click chemistry of dimeric metal-salphen complexes (with NiII and PtII) bridged by either polyether or peptide linkers. We show by circular dichroism (CD) spectroscopy that they generally have higher selectivity for dimeric vs monomeric G-quadruplexes. The emissive properties of the PtII-salphen dimeric complexes have been used to study their interactions with monomeric and dimeric G-quadruplexes in vitro as well as to study their cellular uptake and localization.

show abstract

Photo-induced telomeric DNA damage in human cancer cells

Abstract: Novel dinuclear ruthenium(ii) complexes were designed to target and to photo-react with G-quadruplex telomeric DNA. Thanks to a microscopic-based telomere dysfunction assay, we brought the first evidence of G-driven telomeric DNA photo-lesions in cellulo.

Cited by 7 publications

References 39 publications

Ru(II) Phenanthroline-Based Oligothienyl Complexes as Phototherapy Agents

Ru(II) Phenanthroline-Based Oligothienyl Complexes as Phototherapy Agents

Selective, Disruptive Luminescent Ru(II) Polypyridyl Probes of G-Quadruplex

Dimeric Metal-Salphen Complexes Which Target Multimeric G-Quadruplex DNA

Contact Info

Product

Resources

About