Poly(alkylidenimine) Dendrimers Functionalized with the Organometallic Moiety [Ru(η⁵-C₅H₅)(PPh₃)₂]⁺ as Promising Drugs Against Cisplatin-Resistant Cancer Cells and Human Mesenchymal Stem Cells

  • Molecules. 2018 Jun 17;23(6):1471. doi: 10.3390/molecules23061471.
Marisol Gouveia  1 ,  João Figueira  2 ,  Manuel G Jardim  3 ,  Rita Castro  4 ,  Helena Tomás  5 ,  Kari Rissanen  6 ,  João Rodrigues  7  8
Affiliations
  • 1. CQM-Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal. [email protected].
  • 2. Department of Chemistry, ScilifeLab, Umeå University, KBC-Building, Linnaeus väg 6, 90736 Umeå, Sweden. [email protected].
  • 3. CQM-Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal. [email protected].
  • 4. CQM-Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal. [email protected].
  • 5. CQM-Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal. [email protected].
  • 6. Department of Chemistry, University of Jyvaskyla, P.O. Box. 35, FI-40014 Jyväskylä, Finland. [email protected].
  • 7. CQM-Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal. [email protected].
  • 8. School of Materials Science and Engineering/Center for Nano Energy Materials, Northwestern Polytechnical University, Xi'an 710072, China. [email protected].
PMID: 29914219 DOI: 10.3390/molecules23061471
Abstract

Here and for the first time, we show that the organometallic compound [Ru(η⁵-C₅H₅)(PPh₃)₂Cl] (RuCp) has potential to be used as a metallodrug in Anticancer therapy, and further present a new approach for the cellular delivery of the [Ru(η⁵-C₅H₅)(PPh₃)₂]⁺ fragment via coordination on the periphery of low-generation poly(alkylidenimine) dendrimers through nitrile terminal groups. Importantly, both the RuCp and the dendrimers functionalized with [Ru(η⁵-C₅H₅)(PPh₃)₂]⁺ fragments present remarkable toxicity towards a wide set of Cancer cells (Caco-2, MCF-7, CAL-72, and A2780 cells), including cisplatin-resistant human ovarian carcinoma cell lines (A2780cisR cells). Also, RuCp and the prepared metallodendrimers are active against human mesenchymal stem cells (hMSCs), which are often found in the tumor microenvironment where they seem to play a role in tumor progression and drug resistance.

Keywords
cancer treatment; cisplatin; dendrimers; hMSCs; metallodrugs; nanocarriers; nanomedicine; platinum; ruthenium; toxicity.