Guanine-rich DNA sequences can spontaneously fold into four-stranded structures called G-quadruplexes (G4s). G4s have been identified extensively in the promoter regions of several proto-oncogenes, including c-myc, as well as telomeres. G4s have attracted an increasing amount of attention in the field of nanotechnology because of their use as versatile building blocks of DNA-based nanostructures. In this study, we report the self-assembly of c-myc G-quadruplex DNA controlled by a pair of chiral ruthenium(ii) complexes coordinated by 2-(4-phenyacetylenephenyl)-1H-imidazo[4,5f][1,10]phenanthroline (PBEPIP), Λ-[Ru(bpy)2(PBEPIP)](ClO4)2 (Λ-RM0627, bpy = bipyridine) and Δ-[Ru(bpy)2(PBEPIP)](ClO4)2 (Δ-RM0627). Λ-RM0627 could promote the high-order self-assembly of c-myc G-quadruplex DNA into a nanowire structure, whereas Δ-RM0627 could induce DNA condensation into G-quadruplex aggregates. Moreover, in vitro studies on human liver carcinoma HepG2 cells showed that the nanowire of c-myc G-quadruplex DNA promoted by Λ-RM0627 could be localized in the nuclei of cells, whereas the nanoparticle of c-myc G-quadruplex DNA generated by Δ-RM0627 was taken up and localized in the cytoplasm. This study provides examples of the enantioselective self-assembly of G4 DNA molecules controlled by chiral ruthenium(ii) complexes and suggests the potential applications of assembled nanostructures as non-viral DNA vectors for gene therapy.

中文翻译：

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手性Ru（ii）复合物可作为潜在的非病毒基因载体，用于定向转运至细胞核和细胞质。

富含鸟嘌呤的DNA序列可自发折叠成称为G-四链体（G4s）的四链结构。已经在包括c-myc以及端粒的数个原癌基因的启动子区域中广泛鉴定出G4。由于G4用作基于DNA的纳米结构的通用构建基块，因此在纳米技术领域引起了越来越多的关注。在这项研究中，我们报告了由2-（4-苯乙炔基苯基）-1H-咪唑并[4,5f] [1，1]协调的一对手性钌（ii）配合物控制的c-myc G-四链体DNA的自组装。 10]菲咯啉（PBEPIP），Λ-[Ru（bpy）2（PBEPIP）]（ClO4）2（Λ-RM0627，bpy =联吡啶）和Δ-[Ru（bpy）2（PBEPIP）]（ClO4）2（ Δ-RM0627）。Λ-RM0627可以促进c-myc G-四链体DNA的高阶自组装成纳米线结构，而Δ-RM0627可以诱导DNA缩合成G-四链体聚集体。此外，对人肝癌HepG2细胞的体外研究表明，由Λ-RM0627促进的c-myc G-四链体DNA的纳米线可以位于细胞核中，而由c-myc G-四链体DNA产生的纳米颗粒可以定位在细胞核中。吸收Δ-RM0627并定位在细胞质中。这项研究提供了由手性钌（ii）配合物控制的G4 DNA分子对映选择性自组装的实例，并提出了组装后的纳米结构作为基因治疗的非病毒DNA载体的潜在应用。而由Δ-RM0627产生的c-myc G-四链体DNA的纳米颗粒被吸收并定位在细胞质中。这项研究提供了由手性钌（ii）配合物控制的G4 DNA分子对映选择性自组装的实例，并提出了组装后的纳米结构作为基因治疗的非病毒DNA载体的潜在应用。而由Δ-RM0627产生的c-myc G-四链体DNA的纳米颗粒被吸收并定位在细胞质中。这项研究提供了由手性钌（ii）配合物控制的G4 DNA分子对映选择性自组装的实例，并提出了组装后的纳米结构作为基因治疗的非病毒DNA载体的潜在应用。