Rahbani Janane F, Vengut-Climent Empar, Chidchob Pongphak, Gidi Yasser, Trinh Tuan, Cosa Gonzalo, Sleiman Hanadi F
Department of Chemistry, Centre for Self-Assembled Chemical Structures, McGill University, 801 Sherbrooke St. West, Montreal, H3A 0B8, Canada.
Adv Healthc Mater. 2018 Mar;7(6):e1701049. doi: 10.1002/adhm.201701049. Epub 2018 Jan 22.
Natural systems combine different supramolecular interactions in a hierarchical manner to build structures. In contrast, DNA nanotechnology relies almost exclusively on DNA base pairing for structure generation. Introducing other supramolecular interactions can expand the structural and functional range of DNA assemblies, but this requires an understanding of the interplay between these interactions. Here, an economic strategy to build DNA nanotubes functionalized with lipid-like polymers is reported. When these polymers are linked to the nanotube using a spacer, they fold inside to create a hydrophobic environment within the nanotube; the nanotube can encapsulate small molecules and conditionally release them when specific DNA strands are added, as monitored by single-molecule fluorescence microscopy. When the polymers are directly linked to the nanostructure without spacers, they interact intermolecularly to form a network of DNA bundles. This morphological switch can be directly observed using a strand displacement strategy. The two association modes result in different cellular uptake behavior. Nanotubes with internal hydrophobic association show dye-mediated mitochondrial colocalization inside cells; while the bundles disassemble into smaller polymer-coated structures that reduce the extent of nonspecific cellular uptake. This approach uncovers parameters to direct the hierarchical assembly of DNA nanostructures, and produces promising materials for targeted drug delivery.
自然系统以分层的方式结合不同的超分子相互作用来构建结构。相比之下，DNA纳米技术几乎完全依赖DNA碱基配对来生成结构。引入其他超分子相互作用可以扩展DNA组装体的结构和功能范围，但这需要了解这些相互作用之间的相互关系。在此，报道了一种构建用类脂质聚合物功能化的DNA纳米管的经济策略。当这些聚合物通过间隔物连接到纳米管时，它们会在内部折叠，在纳米管内形成疏水环境；纳米管可以封装小分子，并在添加特定DNA链时在单分子荧光显微镜监测下有条件地释放它们。当聚合物不通过间隔物直接连接到纳米结构时，它们会分子间相互作用形成DNA束网络。这种形态转变可以使用链置换策略直接观察到。这两种缔合模式导致不同的细胞摄取行为。具有内部疏水缔合的纳米管在细胞内显示染料介导的线粒体共定位；而束会分解成较小的聚合物包被结构，从而降低非特异性细胞摄取的程度。这种方法揭示了指导DNA纳米结构分层组装的参数，并产生了用于靶向药物递送的有前景的材料。
