Biological membrane channels, considered as molecular gatekeepers, control the transportation of molecules and ions across live cell membranes. Developing synthetic passable channels with predictable structures, high transport efficiency, and low cytotoxicity on live cells is of great interest for replicating the functions of endogenous protein channels, but remains challenging. The development of DNA nanotechnology provides possible solutions for making synthetic channels with precise structures and controllable functionalization. Therefore, in this work, we constructed a phosphorothioate-modified DNA nanopore able to structurally mimic biological channels for molecular transport across live cell membranes. With its stable structure with small hollow size (<2 nm) and the ability to interact with the lipid molecules, this DNA nanopore could show stable insertion into the plasma membrane. We further proved that this membrane-spanning channel could transport ions and antitumor drugs to neurons and cancer cells, respectively, and do so within a certain time window. We expect that this live cell membrane-spanning synthetic DNA nanopore will provide a tool for studying cellular communication, building synthetic cells, and achieving controlled transmembrane transport to cells.

中文翻译：

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通过仿生DNA通道在活细胞膜上的分子运输。

被认为是分子守门员的生物膜通道控制着分子和离子在活细胞膜上的运输。开发具有可预测的结构，高运输效率和对活细胞的低细胞毒性的合成的可通过通道对于复制内源蛋白通道的功能非常重要，但仍然具有挑战性。DNA纳米技术的发展为制造具有精确结构和可控功能的合成通道提供了可能的解决方案。因此，在这项工作中，我们构建了一种硫代磷酸酯修饰的DNA纳米孔，该孔能够在结构上模拟生物分子跨活细胞膜转运的生物通道。凭借其稳定的结构和较小的中空尺寸（<2 nm）以及与脂质分子相互作用的能力，这种DNA纳米孔可以显示出稳定插入质膜的能力。我们进一步证明了该跨膜通道可以将离子和抗肿瘤药物分别转运至神经元和癌细胞，并在一定时间范围内完成。我们希望这种跨活细胞膜的合成DNA纳米孔将为研究细胞通讯，构建合成细胞并实现跨膜向细胞的受控转运提供工具。