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

• Main Authors: Marisol Gouveia, João Figueira, Manuel G. Jardim, Rita Castro, Helena Tomás, Kari Rissanen, João Rodrigues
• Format: Article
• Language: English
• Published: MDPI AG 2018-06-01
• Series: Molecules
• Subjects: dendrimers; nanocarriers; metallodrugs; ruthenium; platinum; cisplatin; cancer treatment; hMSCs; toxicity; nanomedicine
• Online Access: http://www.mdpi.com/1420-3049/23/6/1471
• ISSN: 1420-3049

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.