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.

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.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Caco-2 Cells
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cisplatin / pharmacology*
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Dendrimers
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Screening Assays, Antitumor
  • Epithelial-Mesenchymal Transition / drug effects
  • Humans
  • MCF-7 Cells
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / pharmacology

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Dendrimers
  • Organometallic Compounds
  • eta5-cyclopentadienyl(2,2'-bipyridyl)(triphenylphosphane)ruthenium(II)
  • Cisplatin