Molecular Transport through a Biomimetic DNA Channel on Live Cell Membranes

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.