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Encapsulation of the dinuclear trithiolato-bridged arene ruthenium complex diruthenium-1 in an apoferritin nanocage: structure and cytotoxicity.

ChemMedChem 2019 January 24
The effects of the encapsulation of the cytotoxic dinuclear trithiolato-bridged arene Ru complex [(η6-p-MeC6H4Pri)2Ru2(μ2-S-p-C6H4But)3]Cl (DiRu-1) within the apoferritin (AFt) nanocage were investigated. The DiRu-1-AFt nanocarrier was characterized by UV-Vis spectroscopy, ICP MS, CD and X-ray crystallography. In contrast to previously reported Au- and Pt- based drug-loaded AFt carriers, no direct interactions between DiRu-1 and AFt were evidenced. DiRu-1-AFt is cytotoxic towards immortalized murine fibroblast BALB/c-3T3 transformed with SV40 virus (SVT2) and human epidermoid carcinoma A431 malignant cells and exhibits a moderate selectivity for these cancer cells over the normal BALB/c-3T3 cells. DiRu-1-AFt triggers ROS production, depolarization of mitochondrial membrane potential and induces cell death via p53-mediated apoptosis. The comparison between our data and previous results suggest that the existence of specific interactions between a metal-based drug and AFt within the protein cage is not essential for drug encapsulation.

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