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Metallacarboranes on the Road to Anticancer Therapies: Cellular Uptake, DNA Interaction, and Biological Evaluation of Cobaltabisdicarbollide [COSAN] −
Author(s) -
Fuentes Isabel,
GarcíaMendiola Tania,
Sato Shinichi,
Pita Marcos,
Nakamura Hiroyuki,
Lorenzo Encarnación,
Teixidor Francesc,
Marques Fernanda,
Viñas Clara
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201803178
Subject(s) - biodistribution , chemistry , dna , biophysics , cytotoxicity , mononuclear phagocyte system , cell culture , ionic bonding , in vivo , cell , in vitro , biochemistry , ion , biology , organic chemistry , genetics , microbiology and biotechnology , immunology
After uptake by U87 MG and A375 cancer cells, cobaltabisdicarbollide [COSAN] − distributes between membrane and nucleus and presents no relevant cytotoxicity against both cell lines even for long incubation times. The cytotoxicity of Na[COSAN] was also tested towards one normal cell line, the V79 fibroblasts, in order to ascertain the noncytotoxic profile of the compound. As the cell's nucleus contains DNA, the interaction between [COSAN] − and double‐stranded calf thymus DNA (CT‐ ds DNA) has been investigated. There is a strong interaction between both molecules forming a nanohybrid CT‐ ds DNA‐[COSAN] biomaterial, which was fully characterized. Moreover, Na[COSAN] shows characteristic redox peaks ascribed to the oxidation/reduction of Co 3+/2+ at a formal potential of −1.444 V and it can be accumulated at a surface‐immobilized DNA layer of glassy carbon electrodes. The equilibrium surface‐binding constants ( K ox / K red ), which confirm that [COSAN] − interacts with DNA by an intercalative or electrostatic mode, depending on the ionic strength of the solution, were estimated. In addition, high binding affinity of Na[COSAN] to proteins was observed by 11 B{ 1 H} NMR and confirmed in vivo. Finally, biodistribution studies of [COSAN] − in normal mice were run. After administration, Na[COSAN] was distributed into many organs but mainly accumulated in the reticuloendothelial system (RES), including liver and spleen. After 1 h, the formation of aggregates by plasma protein interaction plays a role in the biodistribution profile; the aggregates accumulate mostly in the lungs. Na[COSAN], which displays low toxicity and high uptake by relevant cancer cells accumulating boron within the nucleus, could act as a suitable compound for further developments as boron neutron capture therapy (BNCT) agents.