Metallacarboranes on the Road to Anticancer Therapies: Cellular Uptake, DNA Interaction, and Biological Evaluation of Cobaltabisdicarbollide [COSAN]

Isabel Fuentes, Tania García-Mendiola, Shinichi Sato, Marcos Pita, Hiroyuki Nakamura, Encarnación Lorenzo, Francesc Teixidor, Fernanda Marques, Clara Viñas

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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-dsDNA) has been investigated. There is a strong interaction between both molecules forming a nanohybrid CT-dsDNA-[COSAN] biomaterial, which was fully characterized. Moreover, Na[COSAN] shows characteristic redox peaks ascribed to the oxidation/reduction of Co3+/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 (Kox/Kred), 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 11B{1H} 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.

Original languageEnglish
Pages (from-to)17239-17254
Number of pages16
JournalChemistry - A European Journal
Volume24
Issue number65
DOIs
Publication statusPublished - 2018 Nov 22
Externally publishedYes

Keywords

  • DNA recognition
  • antitumor agents
  • boron neutron capture therapy (BNCT)
  • intercalations
  • metallacarboranes
  • redox chemistry

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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