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BioMetals

, Volume 31, Issue 4, pp 517–525 | Cite as

The cluster [Re6Se8I6]3− penetrates biological membranes: drug-like properties for CNS tumor treatment and diagnosis

  • Lisbell D. Estrada
  • Elizabeth Duran
  • Matias Cisterna
  • Cesar Echeverria
  • Zhiping Zheng
  • Vincenzo Borgna
  • Nicolas Arancibia-Miranda
  • Rodrigo Ramírez-Tagle
Article
  • 104 Downloads

Abstract

Tumorigenic cell lines are more susceptible to [Re6Se8I6]3− cluster-induced death than normal cells, becoming a novel candidate for cancer treatment. Still, the feasibility of using this type of molecules in human patients remains unclear and further pharmacokinetics analysis is needed. Using coupled plasma optical emission spectroscopy, we determined the Re-cluster tissue content in injected mice, as a biodistribution measurement. Our results show that the Re-cluster successfully reaches different tissues, accumulating mainly in heart and liver. In order to dissect the mechanism underlying cluster biodistribution, we used three different experimental approaches. First, we evaluate the degree of lipophilicity by determining the octanol/water partition coefficient. The cluster mostly remained in the octanol fraction, with a coefficient of 1.86 ± 0.02, which indicates it could potentially cross cell membranes. Then, we measured the biological membrane penetration through a parallel artificial membrane permeability assays (PAMPA) assay. The Re-cluster crosses the artificial membrane, with a coefficient of 122 nm/s that is considered highly permeable. To evaluate a potential application of the Re-cluster in central nervous system (CNS) tumors, we analyzed the cluster’s brain penetration by exposing cultured blood–brain-barrier (BBB) cells to increasing concentrations of the cluster. The Re-cluster effectively penetrates the BBB, reaching nearly 30% of the brain side after 24 h. Thus, our results indicate that the Re-cluster penetrates biological membranes reaching different target organs—most probably due to its lipophilic properties—becoming a promising anti-cancer drug with high potential for CNS cancer’s diagnosis and treatment.

Keywords

Cluster Blood–brain barrier (BBB) Brain Tumors Cancer 

Notes

Acknowledgements

This work was supported by Fondecyt 11130007 to RR-T and Fondecyt 11130561 to LDE.

Compliance with ethical standards

Conflicts of interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Lisbell D. Estrada
    • 1
  • Elizabeth Duran
    • 1
  • Matias Cisterna
    • 1
  • Cesar Echeverria
    • 1
  • Zhiping Zheng
    • 2
  • Vincenzo Borgna
    • 3
    • 4
  • Nicolas Arancibia-Miranda
    • 5
    • 6
  • Rodrigo Ramírez-Tagle
    • 7
  1. 1.Centro de Biología y Química Aplicada (CIBQA)Universidad Bernardo O HigginsSantiagoChile
  2. 2.Department of ChemistryThe University of ArizonaTucsonUSA
  3. 3.Urology DepartmentHospital Barros Luco TrudeauSantiagoChile
  4. 4.Andes Biotechnologies SA and Fundación Ciencia para la VidaSantiagoChile
  5. 5.Facultad de Química y BiologiaUniversidad de Santiago de ChileSantiagoChile
  6. 6.Center of Development of Nanoscience and Nanotechnology CEDENNASantiagoChile
  7. 7.Facultad de Ingeniería Ciencia y TecnologíaUniversidad Bernardo O HigginsSantiagoChile

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