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

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 specie...

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Autores principales: Ramos, L.C.B., Rodrigues, F.P., Biazzotto, J.C., de Paula Machado, S., Slep, L.D., Hamblin, M.R., da Silva, R.S.
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Acceso en línea:http://hdl.handle.net/20.500.12110/paper_09498257_v23_n6_p903_Ramos
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spelling todo:paper_09498257_v23_n6_p903_Ramos2023-10-03T15:49:36Z Targeting the mitochondrial VDAC in hepatocellular carcinoma using a polyclonal antibody-conjugated to a nitrosyl ruthenium complex Ramos, L.C.B. Rodrigues, F.P. Biazzotto, J.C. de Paula Machado, S. Slep, L.D. Hamblin, M.R. da Silva, R.S. Conjugated ruthenium-antibody complex Nitric oxide delivery agent Nitrosyl ruthenium complexes 2,2' bipyridine derivative antibody drug conjugate cell surface marker dicarboxylic acid derivative immunoglobulin G antibody nitric oxide ruthenium complex voltage dependent anion channel animal cell animal experiment animal tissue antineoplastic activity Article cell surface comparative study controlled study cytotoxicity density functional theory drug targeting Hep-G2 cell line liver cell carcinoma male nonhuman priority journal protein targeting rat 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-[RuII(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-[RuII(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-[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 by NO release. © 2018, SBIC. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09498257_v23_n6_p903_Ramos
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Conjugated ruthenium-antibody complex
Nitric oxide delivery agent
Nitrosyl ruthenium complexes
2,2' bipyridine derivative
antibody drug conjugate
cell surface marker
dicarboxylic acid derivative
immunoglobulin G antibody
nitric oxide
ruthenium complex
voltage dependent anion channel
animal cell
animal experiment
animal tissue
antineoplastic activity
Article
cell surface
comparative study
controlled study
cytotoxicity
density functional theory
drug targeting
Hep-G2 cell line
liver cell carcinoma
male
nonhuman
priority journal
protein targeting
rat
spellingShingle Conjugated ruthenium-antibody complex
Nitric oxide delivery agent
Nitrosyl ruthenium complexes
2,2' bipyridine derivative
antibody drug conjugate
cell surface marker
dicarboxylic acid derivative
immunoglobulin G antibody
nitric oxide
ruthenium complex
voltage dependent anion channel
animal cell
animal experiment
animal tissue
antineoplastic activity
Article
cell surface
comparative study
controlled study
cytotoxicity
density functional theory
drug targeting
Hep-G2 cell line
liver cell carcinoma
male
nonhuman
priority journal
protein targeting
rat
Ramos, L.C.B.
Rodrigues, F.P.
Biazzotto, J.C.
de Paula Machado, S.
Slep, L.D.
Hamblin, M.R.
da Silva, R.S.
Targeting the mitochondrial VDAC in hepatocellular carcinoma using a polyclonal antibody-conjugated to a nitrosyl ruthenium complex
topic_facet Conjugated ruthenium-antibody complex
Nitric oxide delivery agent
Nitrosyl ruthenium complexes
2,2' bipyridine derivative
antibody drug conjugate
cell surface marker
dicarboxylic acid derivative
immunoglobulin G antibody
nitric oxide
ruthenium complex
voltage dependent anion channel
animal cell
animal experiment
animal tissue
antineoplastic activity
Article
cell surface
comparative study
controlled study
cytotoxicity
density functional theory
drug targeting
Hep-G2 cell line
liver cell carcinoma
male
nonhuman
priority journal
protein targeting
rat
description 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-[RuII(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-[RuII(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-[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 by NO release. © 2018, SBIC.
format JOUR
author Ramos, L.C.B.
Rodrigues, F.P.
Biazzotto, J.C.
de Paula Machado, S.
Slep, L.D.
Hamblin, M.R.
da Silva, R.S.
author_facet Ramos, L.C.B.
Rodrigues, F.P.
Biazzotto, J.C.
de Paula Machado, S.
Slep, L.D.
Hamblin, M.R.
da Silva, R.S.
author_sort Ramos, L.C.B.
title Targeting the mitochondrial VDAC in hepatocellular carcinoma using a polyclonal antibody-conjugated to a nitrosyl ruthenium complex
title_short Targeting the mitochondrial VDAC in hepatocellular carcinoma using a polyclonal antibody-conjugated to a nitrosyl ruthenium complex
title_full Targeting the mitochondrial VDAC in hepatocellular carcinoma using a polyclonal antibody-conjugated to a nitrosyl ruthenium complex
title_fullStr Targeting the mitochondrial VDAC in hepatocellular carcinoma using a polyclonal antibody-conjugated to a nitrosyl ruthenium complex
title_full_unstemmed Targeting the mitochondrial VDAC in hepatocellular carcinoma using a polyclonal antibody-conjugated to a nitrosyl ruthenium complex
title_sort targeting the mitochondrial vdac in hepatocellular carcinoma using a polyclonal antibody-conjugated to a nitrosyl ruthenium complex
url http://hdl.handle.net/20.500.12110/paper_09498257_v23_n6_p903_Ramos
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