CQM-Centro de Química da Madeira, MMRG, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal.
Department of Chemistry, ScilifeLab, Umeå University, KBC-Building, Linnaeus väg 6, 90736 Umeå, Sweden.
Molecules. 2018 Jun 17;23(6):1471. doi: 10.3390/molecules23061471.
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 (A2780R 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.
本文首次表明,有机金属化合物[Ru(η⁵-C₅H₅)(PPh₃)₂Cl](RuCp)具有作为抗癌治疗金属药物的潜力,并进一步提出了一种通过末端氰基基团在低代聚(亚烷基)树枝状大分子的外围配位将[Ru(η⁵-C₅H₅)(PPh₃)₂]⁺片段递送至细胞内的新方法。重要的是,既带有 RuCp 的又带有[Ru(η⁵-C₅H₅)(PPh₃)₂]⁺片段的树枝状大分子对广泛的癌细胞(Caco-2、MCF-7、CAL-72 和 A2780 细胞),包括顺铂耐药的人卵巢癌细胞系(A2780R 细胞)都表现出显著的毒性。此外,RuCp 和制备的金属树枝状大分子对人间充质干细胞(hMSCs)也有活性,hMSCs 通常存在于肿瘤微环境中,它们似乎在肿瘤进展和耐药性中发挥作用。