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Molecules 2018, 23(6), 1471; https://doi.org/10.3390/molecules23061471

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

1
CQM—Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal
2
Department of Chemistry, ScilifeLab, Umeå University, KBC-Building, Linnaeus väg 6, 90736 Umeå, Sweden
3
Department of Chemistry, University of Jyvaskyla, P.O. Box. 35, FI-40014 Jyväskylä, Finland
4
School of Materials Science and Engineering/Center for Nano Energy Materials, Northwestern Polytechnical University, Xi’an 710072, China
*
Author to whom correspondence should be addressed.
Received: 5 May 2018 / Revised: 11 June 2018 / Accepted: 12 June 2018 / Published: 17 June 2018
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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. View Full-Text
Keywords: dendrimers; nanocarriers; metallodrugs; ruthenium; platinum; cisplatin; cancer treatment; hMSCs; toxicity; nanomedicine dendrimers; nanocarriers; metallodrugs; ruthenium; platinum; cisplatin; cancer treatment; hMSCs; toxicity; nanomedicine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Gouveia, M.; Figueira, J.; Jardim, M.G.; Castro, R.; Tomás, H.; Rissanen, K.; Rodrigues, J. 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, 23, 1471.

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