The Effect of Photosensitizer Metalation Incorporated into Arene-Ruthenium Assemblies on Prostate Cancer.

Prostate cancer is the second most common cancer for men and a major health issue. Despite treatments, a lot of side effects are observed. Photodynamic therapy is a non-invasive method that uses photosensitizers and light to induce cell death through the intramolecular generation of reactive oxygen species, having almost no side effects. However, some of the PSs used in PDT show inherent low solubility in biological media, and accordingly, functionalization or vectorization is needed to ensure internalization. To this end, we have used arene-ruthenium cages in order to deliver PSs to cancer cells. These metalla-assemblies can host PSs inside their cavity or be constructed with PS building blocks. In this study, we wanted to determine if the addition of metals (Mg, Co, Zn) in the center of these PSs plays a role. Our results show that most of the compounds induce cytotoxic effects on DU 145 and PC-3 human prostate cancer cells. Localization by fluorescence confirms the internalization of the assemblies in the cytoplasm. An analysis of apoptotic processes shows a cleavage of pro-caspase-3 and poly-ADP-ribose polymerase, thus leading to a strong induction of DNA fragmentation. Finally, the presence of metals in the PS decreases PDT's effect and can even annihilate it.

Dimethyl Sulfoxide: A Bio-Friendly or Bio-Hazard Chemical? The Effect of DMSO in Human Fibroblast-like Synoviocytes.

The effect of dimethyl sulfoxide (DMSO) in rheumatoid arthritis (RA) human fibroblast-like synoviocytes (FLSs) has been studied on five different samples harvested from the joints (fingers, hands and pelvis) of five women with RA. At high concentrations (>5%), the presence of DMSO induces the cleavage of caspase-3 and PARP-1, two phenomena associated with the cell death mechanism. Even at a 0.5% concentration of DMSO, MTT assays show a strong toxicity after 24 h exposure (≈25% cell death). Therefore, to ensure a minimum impact of DMSO on RA FLSs, our study shows that the concentration of DMSO has to be below 0.05% to be considered safe.

Ruthenium-based assemblies incorporating tetrapyridylporphyrin panels: a photosensitizer delivery strategy for the treatment of rheumatoid arthritis by photodynamic therapy.

Ruthenium-based assemblies containing tetrapyridylporphyrins (TPyP) in their structure have been evaluated as photosensitizers (PS) to treat rheumatoid arthritis (RA) by photodynamic therapy (PDT). TPyP is useless by itself as a PS due to its low solubility in biological media, however, incorporated in metallacages it can be internalized in cells. The study shows a cellular antiproliferative activity in fibroblast-like synoviocyte (FLS) in the lower nanomolar range in the presence of light, and no dark toxicity at 1 µM concentration, thus having an excellent photoactivity index. The presence of diamagnetic (Zn2+) and paramagnetic (Co2+) metals in the center of TPyP impairs the effectiveness of PDT, showing no (Co) or reduced (Zn) photoactivity. A total of five metallacages with different structural characteristics have been evaluated, and our results suggest that the incorporation of PS in metalla-assemblies is not only an elegant method to increase solubility in biological media for TPyP but also appears to be an efficient hybrid system to treat RA by PDT.

Evaluation of Ruthenium-Based Assemblies as Carriers of Photosensitizers to Treat Rheumatoid Arthritis by Photodynamic Therapy.

For the first time, ruthenium-based assemblies have been used as carriers for photosensitizers in the treatment of rheumatoid arthritis by photodynamic therapy (PDT). These metallacages are totally soluble in physiological media and can transport photosensitizers (PS) in their cavity. After an incubation period, the PS is released in the cytoplasm and irradiation can take place. This strategy allows photosensitizers with low or null solubility in biological media to be evaluated as PDT agents in rheumatoid arthritis. The systems in which 21H,23H-porphine and 29H,31H-phthalocyanine are encapsulated show excellent photocytotoxicity and no toxicity in the dark. On the other hand, systems in which metalated derivatives such as Mg(II)-porphine and Zn(II)-phthalocyanine are used show good photocytotoxicity, but to a lesser extent than the previous two. Furthermore, the presence of Zn(II)-phthalocyanine significantly increases the toxicity of the system. Overall, fifteen different host-guest systems have been evaluated, and based on the results obtained, they show high potential for treating rheumatoid arthritis by PDT.