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.
Highlights
Despite their complexity and diversity, oncologic diseases are mainly characterized by the abnormal growth of cells which can gain the potential to invade tissues and disseminate to distant locations in the body [1,2]
Our results show that RuCp, metallodendrimer 3 and 4 are cytotoxic for cancer cell lines, and for human mesenchymal stem cells (hMSCs), which should contribute to their overall efficiency in anticancer therapeutics
Low-generation ruthenium (II) metallodendrimers based on two nitrile poly(alkylidenimine) dendritic scaffolds and containing at the periphery the organometallic fragment [Ru(η5 -C5 H5 )(PPh3 )2 ]+ were synthesized and characterized
Summary
Despite their complexity and diversity, oncologic diseases are mainly characterized by the abnormal growth of cells which can gain the potential to invade tissues and disseminate (metastasize) to distant locations in the body [1,2]. The discovery of cis-diamminedichloroplatinum (II) (commonly abbreviated as DDP, cisplatin or cisPt) anticancer properties by Rosenberg et al [5] in 1965, as well as its approval by Food and Drug Administration (FDA) to clinical use in 1978, has triggered the investigation of metal complexes as anticancer chemotherapeutic agents [6,7]. Cisplatin and its second and third-generation platinum drug analogues, cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (carboplatin) and Molecules 2018, 23, 1471; doi:10.3390/molecules23061471 www.mdpi.com/journal/molecules [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O0 )platinum(II) (oxaliplatin), respectively, are the only metal complexes currently used in chemotherapeutic regimes of patients with cancer, being employed alone or in combination with other drugs [8,9,10,11,12,13,14,15]. Efforts have been made to develop non-platinum metallodrugs with the same objective [6,7,8,9,10,11,13,14,16,23,27,28,29]
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