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

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.