Cancer treatment with small interfering RNA (siRNA) is one of the most promising new strategies; however, transfection systems that increase its bioavailability and ensure its delivery to the target cell are necessary. Transfection systems may be just vehicular or could contain fragments with anticancer activity that achieves a synergistic effect with siRNA. Cationic carbosilane dendrimers have proved to be powerful tools as non-viral vectors for siRNA in cancer treatment, and their activity might be potentiated by the inclusion of metallic complexes in its dendritic structure. We have herein explored the interaction between Schiff-base carbosilane copper (II) metallodendrimers, and pro-apoptotic siRNAs. The nanocomplexes formed by metallodendrimers and different siRNA have been examined for their zeta potential and size, and by transmission electron microscopy, fluorescence polarisation, circular dichroism, and electrophoresis. The internalisation of dendriplexes has been estimated by flow cytometry and confocal microscopy in a human breast cancer cell line (MCF-7), following the ability of these metallodendrimers to deliver the siRNA into the cell. Finally, in vitro cell viability experiments have indicated effective interactions between Cu (II) dendrimers and pro-apoptotic siRNAs: Mcl-1 and Bcl-2 in breast cancer cells. Combination of the first-generation derivatives with chloride counterions and with siRNA increases the anticancer activity of the dendriplex constructs and makes them a promising non-viral vector.

中文翻译：

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铜（II）金属树状大分​​子与促凋亡siRNA结合作为抗乳腺癌细胞的有前途的策略。

用小干扰RNA（siRNA）进行癌症治疗是最有前途的新策略之一。但是，需要增加其生物利用度并确保其传递至靶细胞的转染系统。转染系统可能只是车辆，也可能包含具有抗癌活性的片段，可与siRNA发挥协同作用。阳离子碳硅烷树状大分子已被证明是用于治疗癌症的siRNA的非病毒载体的强大工具，并且其树突结构中包含金属配合物可能会增强其活性。我们在这里探索了席夫碱碳硅烷铜（II）金属树枝状大分子与促凋亡siRNA之间的相互作用。研究了由金属树枝状大分子和不同siRNA形成的纳米复合物的zeta电位和大小，并通过透射电子显微镜，荧光偏振，圆二色性和电泳。继这些金属树状大分​​子将siRNA传递到细胞中的能力之后，已经通过流式细胞术和共聚焦显微镜在人乳腺癌细胞系（MCF-7）中估计了树状双链体的内部化。最后，体外细胞活力实验表明，乳腺癌细胞中Cu（II）树状大分子与促凋亡siRNA Mcl-1和Bcl-2之间有效相互作用。第一代衍生物与氯离子抗衡离子和siRNA的结合增加了树状复合体构建体的抗癌活性，并使它们成为有前途的非病毒载体。继这些金属树状大分​​子将siRNA传递到细胞中的能力之后，已经通过流式细胞术和共聚焦显微镜在人乳腺癌细胞系（MCF-7）中估计了树状双链体的内部化。最后，体外细胞生存力实验表明，乳腺癌细胞中Cu（II）树状大分子与促凋亡siRNA Mcl-1和Bcl-2之间有效相互作用。第一代衍生物与氯离子抗衡离子和siRNA的结合增加了树状复合体构建体的抗癌活性，使其成为有前途的非病毒载体。继这些金属树状大分​​子将siRNA传递到细胞中的能力之后，已经通过流式细胞术和共聚焦显微镜在人乳腺癌细胞系（MCF-7）中估计了树状双链体的内部化。最后，体外细胞活力实验表明，乳腺癌细胞中Cu（II）树状大分子与促凋亡siRNA Mcl-1和Bcl-2之间有效相互作用。第一代衍生物与氯离子抗衡离子和siRNA的结合增加了树状复合体构建体的抗癌活性，并使它们成为有前途的非病毒载体。体外细胞活力实验表明，乳腺癌细胞中Cu（II）树状大分子与促凋亡siRNA Mcl-1和Bcl-2之间存在有效的相互作用。第一代衍生物与氯离子抗衡离子和siRNA的结合增加了树状复合体构建体的抗癌活性，并使它们成为有前途的非病毒载体。体外细胞活力实验表明，乳腺癌细胞中Cu（II）树状大分子与促凋亡siRNA Mcl-1和Bcl-2之间存在有效的相互作用。第一代衍生物与氯离子抗衡离子和siRNA的结合增加了树状复合体构建体的抗癌活性，使其成为有前途的非病毒载体。