The cell-impermeable Ru(II) polypyridyl complex as a potent intracellular photosensitizer under visible light irradiation via ion-pairing with suitable lipophilic counter-anions

Yan, Zhu-Ying; Chen, Jing; Shao, Jie; Jiao, Zeqing; Tang, Tian-Shu; Tang, Miao; Sheng, Zhenfeng; Mao, Li; Huang, Rong; Huang, Chunhua; Zhang, Zhihui; Su, Hongmei; Zhu, Ben-Zhan

doi:10.1016/j.freeradbiomed.2021.04.035

Cited by 9 publications

(5 citation statements)

References 79 publications

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“…In short, the enantio-selective induction of cell apoptosis and mtDNA damage were observed for the two chiral form (Δ- and Λ-) of [Ru(phen) 2 (dppz)]Cl 2 complex upon visible light irradiation, with Δ-enantiomer showing much stronger effects compared with Λ-enantiomer. We speculated that the cellular photo-toxicity was induced by ROS (probably 1 O 2 ), which was produced by [Ru(phen) 2 (dppz)]Cl 2 ( 42 , 77 ). As we know, the diffusion distance and lifetime of ROS is short.…”

Section: Resultsmentioning

confidence: 99%

Unprecedented enantio-selective live-cell mitochondrial DNA super-resolution imaging and photo-sensitizing by the chiral ruthenium polypyridyl DNA “light-switch”

Huang,

Chen

et al. 2023

Nucleic Acids Research

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Mitochondrial DNA (mtDNA) is known to play a critical role in cellular functions. However, the fluorescent probe enantio-selectively targeting live-cell mtDNA is rare. We recently found that the well-known DNA ‘light-switch’ [Ru(phen)2dppz]Cl2 can image nuclear DNA in live-cells with chlorophenolic counter-anions via forming lipophilic ion-pairing complex. Interestingly, after washing with fresh-medium, [Ru(phen)2dppz]Cl2 was found to re-localize from nucleus to mitochondria via ABC transporter proteins. Intriguingly, the two enantiomers of [Ru(phen)2dppz]Cl2 were found to bind enantio-selectively with mtDNA in live-cells not only by super-resolution optical microscopy techniques (SIM, STED), but also by biochemical methods (mitochondrial membrane staining with Tomo20-dronpa). Using [Ru(phen)2dppz]Cl2 as the new mtDNA probe, we further found that each mitochondrion containing 1–8 mtDNA molecules are distributed throughout the entire mitochondrial matrix, and there are more nucleoids near nucleus. More interestingly, we found enantio-selective apoptotic cell death was induced by the two enantiomers by prolonged visible light irradiation, and in-situ self-monitoring apoptosis process can be achieved by using the unique ‘photo-triggered nuclear translocation’ property of the Ru complex. This is the first report on enantio-selective targeting and super-resolution imaging of live-cell mtDNA by a chiral Ru complex via formation and dissociation of ion-pairing complex with suitable counter-anions.

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Section: Resultsmentioning

confidence: 99%

Unprecedented enantio-selective live-cell mitochondrial DNA super-resolution imaging and photo-sensitizing by the chiral ruthenium polypyridyl DNA “light-switch”

Huang,

Chen

et al. 2023

Nucleic Acids Research

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“…The investigated RPCs also displayed good capacities to be internalized by A2780 cancer compared to non-cancer cells, with Ru1 2+ and Ru2 2+ being the most effective. This result is of great interest, especially considering that similar RPCs-based PSs were shown to poorly penetrate the cell membrane, and additional expedients, such as ion pairing with suitable lipophilic counter-anions, were necessary to augment the cellular uptake [ 35 ]. In the present study, it is reasonable to assume that the significant cellular uptake by cancer cells is associated with the presence of the polyamino macrocyclic frameworks L’ and L’’ of the Ru(II) compounds, which may impart optimal chemical–physical features for cellular internalization, such as hydrophilicity and total charge of the compounds.…”

Section: Discussionmentioning

confidence: 99%

Highly Charged Ru(II) Polypyridyl Complexes as Photosensitizer Agents in Photodynamic Therapy of Epithelial Ovarian Cancer Cells

Conti

Giacomazzo

Valtancoli

et al. 2022

IJMS

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Ovarian cancer recurrence is frequent and associated with chemoresistance, leading to extremely poor prognosis. Herein, we explored the potential anti-cancer effect of a series of highly charged Ru(II)-polypyridyl complexes as photosensitizers in photodynamic therapy (PDT), which were able to efficiently sensitize the formation of singlet oxygen upon irradiation (Ru12+ and Ru22+) and to produce reactive oxygen species (ROS) in their corresponding dinuclear metal complexes with the Fenton active Cu(II) ion/s ([CuRu1]4+ and [Cu2Ru2]6+). Their cytotoxic and anti-tumor effects were evaluated on human ovarian cancer A2780 cells both in the absence or presence of photoirradiation, respectively. All the compounds tested were well tolerated under dark conditions, whereas they switched to exert anti-tumor activity following photoirradiation. The specific effect was mediated by the onset of programed cell death, but only in the case of Ru12+ and Ru22+ was preceded by the loss of mitochondrial membrane potential soon after photoactivation and ROS production, thus supporting the occurrence of apoptosis via type II photochemical reactions. Thus, Ru(II)-polypyridyl-based photosensitizers represent challenging tools to be further investigated in the identification of new therapeutic approaches to overcome the innate chemoresistance to platinum derivatives of some ovarian epithelial cancers and to find innovative drugs for recurrent ovarian cancer.

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“…Leaf tissues from control and cold-treated rice seedlings for the mutants ( top6a3 and top6b ), the double overexpressing line ( TOP6A3-OE1 TOP6B-OE1 ) and their WT (K3) siblings, were used for preparation of nuclei. A single-cell gel electrophoresis assay (Comet) for DSB detection was performed with a commercial kit (CTCC-M001) as described previously ( 42 , 43 ). Nuclear lysis was performed at 4°C for 1 h instead of at room temperature for 20 min.…”

Section: Methodsmentioning

confidence: 99%

Cold-induced inhibition of photosynthesis-related genes integrated by a TOP6 complex in rice mesophyll cells

Zhang

Wang

et al. 2023

Nucleic Acids Research

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Photosynthesis is the most temperature-sensitive process in the plant kingdom, but how the photosynthetic pathway responds during low-temperature exposure remains unclear. Herein, cold stress (4°C) induced widespread damage in the form DNA double-stranded breaks (DSBs) in the mesophyll cells of rice (Oryza sativa), subsequently causing a global inhibition of photosynthetic carbon metabolism (PCM) gene expression. Topoisomerase genes TOP6A3 and TOP6B were induced at 4°C and their encoded proteins formed a complex in the nucleus. TOP6A3 directly interacted with KU70 to inhibit its binding to cold-induced DSBs, which was facilitated by TOP6B, finally blocking the loading of LIG4, a component of the classic non-homologous end joining (c-NHEJ) pathway. The repression of c-NHEJ repair imposed by cold extended DSB damage signaling, thus prolonging the inhibition of photosynthesis in leaves. Furthermore, the TOP6 complex negatively regulated 13 crucial PCM genes by directly binding to their proximal promoter regions. Phenotypically, TOP6A3 overexpression exacerbated the γ-irradiation-triggered suppression of PCM genes and led to the hypersensitivity of photosynthesis parameters to cold stress, dependent on the DSB signal transducer ATM. Globally, the TOP6 complex acts as a signal integrator to control PCM gene expression and synchronize cold-induced photosynthesis inhibition, which modulates carbon assimilation rates immediately in response to changes in ambient temperature.

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The cell-impermeable Ru(II) polypyridyl complex as a potent intracellular photosensitizer under visible light irradiation via ion-pairing with suitable lipophilic counter-anions

Cited by 9 publications

References 79 publications

Unprecedented enantio-selective live-cell mitochondrial DNA super-resolution imaging and photo-sensitizing by the chiral ruthenium polypyridyl DNA “light-switch”

Unprecedented enantio-selective live-cell mitochondrial DNA super-resolution imaging and photo-sensitizing by the chiral ruthenium polypyridyl DNA “light-switch”

Highly Charged Ru(II) Polypyridyl Complexes as Photosensitizer Agents in Photodynamic Therapy of Epithelial Ovarian Cancer Cells

Cold-induced inhibition of photosynthesis-related genes integrated by a TOP6 complex in rice mesophyll cells

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