Littérature scientifique sur le sujet « Arene-Ruthenium assemblies »

This review article covers the synthetic strategies, structural aspects, and host-guest properties of ruthenium metalla-assemblies, with a special focus on their use as drug delivery vectors. The two-dimensional metalla-rectangles show interesting host-guest possibilities but seem less appropriate for being used as drug carriers. On the other hand, metalla-prisms allow encapsulation and possible targeted release of bioactive molecules and consequently show some potential as drug delivery vectors. The reactivity of these metalla-prisms can be fine-tuned to allow a fine control of the guest’s release. The larger metalla-cubes can be used to stabilize the formation of G-quadruplex DNA and can be used to encapsulate and release photoactive molecules such as porphins. These metalla-assemblies demonstrate great prospective in photodynamic therapy.

The synthesis and characterization of three metalla-rectangles of the general formula [Ru4(η6-p-cymene)4(μ4-clip)2(μ2-Lanthr)2][CF3SO3]4 (Lanthr: 9,10-bis(3,3’-ethynylpyridyl) anthracene; clip = oxa: oxalato; dobq: 2,5-dioxido-1,4-benzoquinonato; donq: 5,8-dioxido-1,4-naphthoquinonato) are presented. The molecular structure of the metalla-rectangle [Ru4(η6-p-cymene)4(μ4-oxa)2(μ2-Lanthr)2]4+ has been confirmed by the single-crystal X-ray structure analysis of [Ru4(η6-p-cymene)4(μ4-oxa)2(μ2-Lanthr)2][CF3SO3]4 · 4 acetone (A2 · 4 acetone), thus showing the anthracene moieties to be available for reaction with oxygen. While the formation of the endoperoxide form of Lanthr was observed in solution upon white light irradiation, the same reaction does not occur when Lanthr is part of the metalla-assemblies.

Colorectal cancer (CRC) is the third most common cancer in the world, with an ongoing rising incidence. Despite secure advancements in CRC treatments, challenges such as side effects and therapy resistance remain to be addressed. Photodynamic therapy (PDT) emerges as a promising modality, clinically used in treating different diseases, including cancer. Among the main challenges with current photosensitizers (PS), hydrophobicity and low selective uptake by the tumor remain prominent. Thus, developing an optimal design for PS to improve their solubility and enhance their selective accumulation in cancer cells is crucial for enhancing the efficacy of PDT. Targeted photoactivation triggers the production of reactive oxygen species (ROS), which promote oxidative stress within cancer cells and ultimately lead to their death. Ruthenium (Ru)-based compounds, known for their selective toxicity towards cancer cells, hold potential as anticancer agents. In this study, we investigated the effect of two distinct arene-Ru assemblies, which lodge porphin PS in their inner cavity, and tested them as PDT agents on the HCT116 and HT-29 human CRC cell lines. The cellular internalization of the porphin-loaded assemblies was confirmed by fluorescence microscopy. Additionally, significant photocytotoxicity was observed in both cell lines after photoactivation of the porphin in the cage systems, inducing apoptosis through caspase activation and cell cycle progression disruptions. These findings suggest that arene-Ru assemblies lodging porphin PS are potent candidates for PDT of CRC.

Le cancer colorectal (CCR) est le troisième cancer le plus fréquent dans le monde et son incidence ne cesse d'augmenter. Malgré des avancées dans les traitements du CCR, des défis tels que les effets secondaires et la résistance aux thérapies restent à relever. La thérapie photodynamique (PDT) apparaît comme une modalité prometteuse, utilisée cliniquement dans le traitement de différentes maladies, dont le cancer. Elle repose sur l'utilisation de molécules photosensibles appelées photosensibilisateurs (PSs), suivie d'une photoactivation par illumination des tissus malades. Les PSs peuvent être conçus pour s'accumuler spécifiquement dans les cellules cancéreuses, ce qui permet lors de leur photoactivation ciblée de déclencher la production d'espèces réactives de l'oxygène. Cela provoquera un stress oxydatif conduisant à la mort cellulaire. Les composés à base de ruthénium (Ru), connus pour leur toxicité sélective à l'égard des cellules cancéreuses, ont un potentiel en tant qu'agents anticancéreux. Dans cette étude, nous avons évalué l'effet de deux assemblages arène-Ru distincts, hébergeant des porphines dans leur cavité interne, comme agents de PDT sur les lignées cellulaires humaines HCT116 et HT-29 de CCR. L'internalisation et la localisation cellulaire des assemblages chargés de porphine ont été confirmées par microscopie à fluorescence. De plus, une photocytotoxicité significative a été observée dans les deux lignées cellulaires après la photoactivation de la porphine dans les systèmes de cages, perturbant la progression du cycle cellulaire et induisant l'apoptose par l'induction de la voie apoptotique mitochondriale avec activation de la caspase-3. Ces résultats suggèrent que les assemblages arène-Ru hébergeant un PS sont des candidats potentiels pour le traitement du CCR
________________________________________Colorectal cancer (CRC) is the third most common cancer in the world with an ongoing rising incidence. Despite advances in CRC treatments, challenges such as side effects and therapy resistance remain to be addressed. Photodynamic therapy (PDT) emerges as a promising modality, clinically used in treating different diseases, including cancer. It is based on the use of photosensitive molecules called photosensitizers (PSs), followed by photoactivation through illumination of the diseased tissues. The PSs can be designed to specifically accumulate in cancer cells, enabling their targeted photoactivation to trigger the production of reactive oxygen species. This will cause oxidative stress leading to cell death. Ruthenium (Ru)-based compounds, known for their selective toxicity towards cancer cells, hold potential as anti-cancer agents. In this study, we investigated the effect of two distinct arene-Ru assemblies lodging porphin in their inner cavity, as PDT agents on HCT116 and HT-29 human CRC cell lines. The cellular internalization and localization of the porphin-loaded assemblies were confirmed by fluorescence microscopy. Additionally, significant photocytotoxicity was observed in both cell lines after photoactivation of the porphin in the cage systems, disrupting the cell cycle progression and inducing apoptosis through induction of the mitochondrial apoptotic pathway with caspase-3 activation. These findings suggest that arene-Ru assemblies lodging a PS are potent candidates for CRC treatment