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Labelled micelles for the delivery of cytotoxic Cu(II) and Ru(III) compounds in the treatment of aggressive orphan cancers: Design and biological in vitro data
Journal of Inorganic Biochemistry ( IF 3.9 ) Pub Date : 2020-10-02 , DOI: 10.1016/j.jinorgbio.2020.111259
Leonardo Brustolin 1 , Nicolò Pettenuzzo 1 , Chiara Nardon 2 , Santina Quarta 3 , Isabella Montagner 4 , Patrizia Pontisso 3 , Antonio Rosato 4 , Pierfranco Conte 4 , Stefano Merigliano 5 , Dolores Fregona 2
Affiliation  

A recent study on our metal-dithiocarbamato complexes pointed out the antiproliferative properties and the druglikeness of some new patented derivatives. In this work, the best compounds have been encapsulated in micellar nanocarriers, being also carbohydrate-functionalized on their hydrophilic surface to investigate the possibility of a cancer-selective delivery. In particular, the nonionic block copolymer Pluronic® F127 (PF127) has been chemically modified with sugars and the derivatives characterized by means of NMR spectroscopy and FT-IR spectrophotometry. Then, the two selected complexes (β-[Ru2(PipeDTC)5]Cl (PipeDTC = piperidine dithiocarbamate) and [Cu(ProOMeDTC)2] (ProOMeDTC = L-proline methyl ester dithiocarbamate)), have been loaded into the hydrophobic core of PF127 micelles and cancer-targeting counterparts. These nanoformulations have been studied for their dimensions (DLS, TEM) and stability, and tested for their cytotoxicity against aggressive human cancer cell lines. The in vitro results were paralleled with mechanistic studies through Confocal Laser Scanning Microscopy and xCELLigence analysis.



中文翻译:

标记的胶束,用于在侵略性孤儿癌症的治疗中递送细胞毒性的Cu(II)和Ru(III)化合物:设计和体外生物学数据

最近对我们的金属-二硫代氨基甲酸酯配合物的研究指出了某些新的专利衍生物的抗增殖特性和药物似性。在这项工作中,最好的化合物已被封装在胶束纳米载体中,并且还在其亲水性表面上被碳水化合物官能化,以研究癌症选择性递送的可能性。尤其是,非离子嵌段共聚物F127(PF127)已用糖和衍生物进行了化学修饰,并通过NMR光谱学和FT-IR光谱学进行了表征。然后,选择了两个络合物(β-[Ru 2(PipeDTC)5 ] Cl(PipeDTC =哌啶二硫代氨基甲酸酯)和[Cu(ProOMeDTC)2](ProOMeDTC = L-脯氨酸甲酯二硫代氨基甲酸酯))已被装入PF127胶束和靶向癌症的对应物的疏水核中。研究了这些纳米制剂的尺寸(DLS,TEM)和稳定性,并测试了它们对侵袭性人类癌细胞系的细胞毒性。该体外结果通过激光共聚焦显微镜和xCELLigence分析机制的研究呈平行关系。

更新日期:2020-10-08
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