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

用有机金属部分 [Ru(η⁵-C₅H₅)(PPh₃)₂]⁺ 功能化的聚(亚烷基亚胺)树枝状聚合物可作为对抗顺铂耐药癌细胞和人类间充质干细胞的有希望的药物

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作者:Marisol Gouveia, João Figueira, Manuel G Jardim, Rita Castro, Helena Tomás, Kari Rissanen, João Rodrigues

Abstract

Here and for the first time, we show that the organometallic compound [Ru(η&sup5;-C₅H₅)(PPh&sub3;)&sub2;Cl] (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(η&sup5;-C₅H₅)(PPh&sub3;)&sub2;]⁺ 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(η&sup5;-C₅H₅)(PPh&sub3;)&sub2;]⁺ 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.

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