Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, China.
Metallomics. 2020 Apr 1;12(4):504-513. doi: 10.1039/c9mt00192a. Epub 2020 Feb 13.
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)(PBEPIP) (Λ-RM0627, bpy = bipyridine) and Δ-Ru(bpy)(PBEPIP) (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.
鸟嘌呤富集的 DNA 序列可以自发折叠成称为 G-四链体 (G4s) 的四链结构。已经在多个原癌基因的启动子区域，包括 c-myc 以及端粒中广泛鉴定出 G4s。由于它们可用作基于 DNA 的纳米结构的多功能构建块，因此 G4s 在纳米技术领域引起了越来越多的关注。在这项研究中，我们报告了由一对手性钌（ii）配合物控制的 c-myc G-四链体 DNA 的自组装，该配合物由 2-(4-苯乙炔基苯基）-1H-咪唑[4,5f][1,10]菲咯啉（PBEPIP）配位，Λ-[Ru(bpy)(PBEPIP)]（ClO）（Λ-RM0627，bpy = 联吡啶）和 Δ-[Ru(bpy)(PBEPIP)]（ClO）（Δ-RM0627）。Λ-RM0627 可以促进 c-myc G-四链体 DNA 高度有序地自组装成纳米线结构，而 Δ-RM0627 可以诱导 DNA 凝聚成 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 的纳米线可以定位于细胞的核内，而由 Δ-RM0627 产生的 c-myc G-四链体 DNA 的纳米颗粒被摄取并定位于细胞质中。这项研究提供了手性钌（ii）配合物控制 G4 DNA 分子对映选择性自组装的实例，并表明组装纳米结构作为非病毒 DNA 载体用于基因治疗的潜在应用。
