Targeting the mitochondrial VDAC in hepatocellular carcinoma using a polyclonal antibody-conjugated to a nitrosyl ruthenium complex

HAMBLIN, M. R. ; BLAZZOTTO, J. C.; DA SILVA, R. S.; MACHADO, S. P.; SLEP, LEONARDO D.; RAMOS, L. C. B.; RODRIGUES, F. P.

JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY

SPRINGER

Lugar: Berlin; Año: 2018 vol. 23 p. 903 - 916

0949-8257

The rational design of anti-cancer agents includes a new approach based on ruthenium complexes that can act as nitricoxide (NO) donor agents against specific cellular targets. One of the most studied classes of those compounds is based onbis(bipyridine) ruthenium fragment and its derivative species. In this work, we present the chemical and cytotoxicity propertiesagainst the liver hepatocellular carcinoma cell line HepG2 of cis-[RuII(NO+)Cl(dcbpy)2]2− conjugated to a polyclonalantibody IgG (anti-VDAC) recognizing a cell surface marker. UV?visible bands of the ruthenium complex were assignedwith the aid of density functional theory, which also allowed estimation of the structures that explain the biological effectsof the ruthenium complex?IgG conjugate. The interaction of cis-[RuII(NO+)Cl(dcbpy)2]3− with mitochondria was evaluateddue to the potential of these organelles as anti-cancer targets, and considering they interact with the anti-VDAC antibody.The cytotoxicity of cis-[RuII(NO+)Cl(dcbpy)2]3−-anti-VDAC antibody was up to 80% greater in comparison to the free cis-[RuII(NO+)Cl(dcbpy)2]3− complex. We suggest that this effect is due to site-specific interaction of the complex followed byNO release.