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

Author(s)

Ramos, Loyanne C. B. ^[1] ; Rodrigues, Fernando P. ^[1] ; Biazzotto, Juliana C. ^[1] ; Machado, Sergio de Paula ^[2] ; Slep, Leonardo D. ^{[3, 4]} ; Hamblin, Michael R. ^{[5, 6]} ; da Silva, Roberto S. ^{[1, 5, 6]}

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Fis & Quim, Ribeirao Preto, SP - Brazil

^[2] Univ Fed Rio de Janeiro, Inst Quim, BR-21941590 Rio De Janeiro, RJ - Brazil

^[3] Univ Buenos Aires, Fac Ciencias Exactas & Nat, CONICET, Dept Quim Inorgan Analit & Quim Fis, Pabellon 2, Ciudad Univ, C1428EHA Buenos Aires, Buenos Aires, DF - Argentina

^[4] Univ Buenos Aires, Fac Ciencias Exactas & Nat, CONICET, INQUIMAE, Pabellon 2, Ciudad Univ, C1428EHA Buenos Aires, Buenos Aires, DF - Argentina

^[5] Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 - USA

^[6] Harvard Med Sch, Dept Dermatol, Boston, MA 02115 - USA

• Document type: Journal article
• Source: JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY; v. 23, n. 6, p. 903-916, AUG 2018.
• Web of Science Citations: 1

Abstract

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

• FAPESP's process: 09/11471-9 - Polyclonal antibody-ruthenium complex interaction as nitric oxide delivery system. Especificity and citotoxic evaluation
• Grantee: Loyanne Carla Barbosa Ramos
• Support Opportunities: Scholarships in Brazil - Master