Horse Spleen Apoferritin‐Encapsulated Organoruthenium Complex Bearing Pyrazolyl–Pyridine Ligand for Cytotoxic and Antimicrobial Resistance Modulations

Horse spleen apoferritin is a highly efficient nanocarrier for encapsulating and delivering metallodrugs, resulting in enhanced stability and therapeutic effectiveness. Herein, Horse spleen apoferritin nanocage(Aftn) is used to encapsulate the model organoruthenium complex bearing a pyrazolyl-pyridine ligand (Ru(bpy)) via a pH-induced disassembly/reassembly method to obtain Ru(bpy)-loaded nanoformulation (Ru-Aftn). This nanoformulation exhibits sustained release of the loaded complex over a period of 6 days with minimal burst release. Ru-Aftn also displays prominent cytotoxicity with better selectivity than the non-encapsulated Ru(bpy) complex against MCF-7 breast cancer cells. AO/EB staining assay revealed that the non-encapsulated complex induced late apoptosis before loading, whereas early apoptosis occurred after being loaded into Aftn. These results support that Aftn can act as a promising carrier for metallodrugs in modulating their molecular mechanism. Nevertheless, it fails to improve the antimicrobial activity of Ru(bpy) when tested against ancomycin-resistant Enterococcus (VRE) strains.