Oxidovanadium complexes with organic ligands are well known to have
cytotoxic or differentiating capabilities against a range of cancer cell
types. Their limited use in clinical testing though has resulted
largely from uncertainties about the long-term toxicities of such
complexes, due in part to the speciation to vanadate ions in the
circulation. We hypothesised that more highly stable complexes,
delivered using liposomes, may provide improved opportunities for
oxidovanadium applications against cancer. In this study we sourced
specifically hydrophobic forms of oxidovanadium complexes with the
explicit aim of demonstrating liposomal encapsulation, bioavailability
in cultured neuroblastoma cells, and effective cytotoxic or
differentiating activity. Our data show that four ethanol-solubilised
complexes with amine bisphenol, aminoalcohol bisphenol or salan ligands
are equally or more effective than a previously used complex
bis(maltolato)oxovanadium(V) in neuroblastoma cell lines. Moreover, we
show that one of these complexes can be stably incorporated into
cationic liposomes where it retains very good bioavailability,
apparently low speciation and enhanced efficacy compared to ethanol
delivery. This study provides the first proof-of-concept that stable,
hydrophobic oxidovanadium complexes retain excellent cellular activity
when delivered effectively to cancer cells with nanotechnology. This
offers the improved prospect of applying oxidovanadium-based drugs in
vivo with increased stability and reduced off-target toxicity.