BioMetals

, Volume 27, Issue 3, pp 507–525 | Cite as

Carriers for metal complexes on tumour cells: the effect of cyclodextrins vs CNTs on the model guest phenanthroline-5,6-dione trithiacyclononane ruthenium(II) chloride

  • Susana S. Braga
  • Joana Marques
  • Elena Heister
  • Cátia V. Diogo
  • Paulo J. Oliveira
  • Filipe A. Almeida Paz
  • Teresa M. Santos
  • Maria Paula M. Marques
Article
First Online:
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Accepted:

Abstract

The complex [Ru[9]aneS3(pdon)Cl]Cl (pdon = 1,10-phenanthroline-5,6-dione) was readily obtained from the stoichiometric reaction of Ru[9]aneS3(dmso)Cl2 with pdon. Recrystallisation in ethanol using salicylic acid as a co-crystallisation helper afforded single-crystals suitable for the collection of X-ray diffraction data which afforded a reasonable structural description. Two different kinds of molecular carriers were tested as vehicles for this complex: carbon nanotubes (CNTs) and cyclodextrins. CNTs had an insufficient loading rate for the ruthenium complex at CNT concentrations deemed non-cytotoxic on cultured cells. The cyclodextrin (CD) carriers, β-CD and TRIMEB (standing for permethylated β-CD), were able to form two adducts, studied by powder X-ray diffraction, thermogravimetric analysis (TGA), 13C{1H} CP/MAS NMR and FT-IR spectroscopies. The DNA thermal denaturation studies showed that the complex 1 is able to intercalate with DNA. The in vitro cytotoxicity of the free complex [Ru[9]aneS3(pdon)Cl]Cl (1) and of its two CD adducts (2 and 3) was assessed on both rodent and human cell lines. By using the mouse K1735-M2 melanoma cell line and the non-tumour rat H9c2 cardiomyoblasts, the results showed that 1 and 2 significantly inhibited the growth of the tumour cell line while displaying a good safety profile on cardiomyoblasts. Compound 3 at 100 μM inhibited the proliferation of both cell lines, with a higher activity towards the melanoma cell line. The cytotoxicity of the compounds 1–3 was further assessed on human breast cancer cell lines. Against the MDA-MB-231 line, growth inhibition occurred only with 1 and 3 at the incubation time of 96 h, both with approximate inhibition rates of 50 %; against the MCF-7 line, mild cytotoxicity was observed at 48 h of incubation, with IC50 values calculated above 100 μM for 1, 2 and 3.

Keywords

Ruthenium complexes 1,10-Phenanthroline-5,6-dione Cyclodextrins Cytotoxicity Carbon nanotubes 

Abbreviations

[9]aneS3

1,4,7-Trithiacyclononane

ANOVA

Analysis of variance

CD

Cyclodextrin

CNT

Carbon nanotube

CP/MAS

Cross-polarisation with magic-angle spinning

DMEM

Dulbecco’s modified eagle’s medium

dmso

Dimethylsulfoxide

DNA

Deoxyribonucleic acid

dppz

Dipyrido[3,2-a:2′,3′-c]phenazine

EDTA

Ethylenediaminetetraacetic acid

EAT

Ehrlich ascites tumour

EtOH

Ethanol

FBS

Fetal bovine serum

FT-IR

Fourier-transform infrared spectroscopy

H9c2

Non-tumoural H9c2 cardiomyoblast cell line

IC50

Half maximal inhibitory concentration

K1735-M2

Mouse melanoma cell line

MCF-7

Human epithelial breast adenocarcinoma cell line (estrogen dependent)

MDA-MB-231

Human epithelial breast adenocarcinoma cell line (estrogen independent)

MTT

3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide

NMR

Nuclear magnetic resonance

oxCNT

Oxidised carbon nanotube

PBS

Phosphate buffered saline

phen

1,10-Phenanthroline

pdon

1,10-Phenanthroline-5,6-dione

SRB

Sulforhodamine B

TGA

Thermogravimetric analysis

XRD

X-ray diffraction

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Notes

Acknowledgments

The supply of β-CD (Kleptose) by Roquette Laboratoires (Lestrem, France) is gracefully acknowledged. We are also grateful to Fundação para a Ciência e a Tecnologia (FCT, Portugal), European Union, QREN, European Fund for Regional Development (FEDER), through the programme COMPETE, for general funding to the QOPNA research unit (project PEst C-QUI/UI0062/2013; FCOMP-01-0124-FEDER-037296), to the Associated Laboratory CICECO (PEst C-CTM/LA0011/2013) and to the CNC (PEst-C/SAU/LA0001/2013-2014), and for specific funding towards the purchase of the single-crystal diffractometer. The FCT and the European Social Fund, through the Programa Operacional Potencial Humano (POPH), are acknowledged for a PhD grant to J. M. (SFRH/BD/44791/2008).

Supplementary material

10534_2014_9725_MOESM1_ESM.doc (246 kb)
Supplementary material 1 (DOC 245 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Susana S. Braga
    • 1
  • Joana Marques
    • 1
  • Elena Heister
    • 2
  • Cátia V. Diogo
    • 3
  • Paulo J. Oliveira
    • 3
  • Filipe A. Almeida Paz
    • 4
  • Teresa M. Santos
    • 4
  • Maria Paula M. Marques
    • 5
  1. 1.Department of Chemistry, QOPNA Research UnitUniversity of AveiroAveiroPortugal
  2. 2.Faculty of Health and Medical SciencesUniversity of SurreyGuildfordUK
  3. 3.CNC - Center for Neuroscience and Cell Biology, Largo Marquês de PombalUniversity of CoimbraCoimbraPortugal
  4. 4.CICECO and Department of ChemistryUniversity of AveiroAveiroPortugal
  5. 5.Molecular Physical-Chemistry R&D Group and Department of Life Sciences, Faculty of Science and TechnologyUniversity of CoimbraCoimbraPortugal

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