In Vivo Dynamic‐Torque Driven DNA Manipulation via a Magnetic Micromotor

ABSTRACT The biological environment in vivo is complex, posing a great challenge for the deployment of DNA nanostructure‐based precision nanomedicine. Despite the development of DNA nanostructures responsive to environmental cues, it remains difficult to manipulate DNA with spatiotemporal precision in vivo. Here, inspired by the mechanical unwinding process of DNA in nature, we propose an in vivo dynamic‐torque driven DNA manipulation strategy enabling DNA structural reconfigurations with minute‐scale temporal resolution and centimeter spatial precision. By coupling the rod‐shaped magnetic micromotors (MMs) with a rotating magnetic field (RMF), this strategy enables mechanical DNA manipulation under a low field strength of 20 mT and extends the working distance by an order of magnitude compared to conventional manipulation methods. By orchestrating the RMF frequency, DNA with distinct force thresholds (12–54 pN) and GC contents (22%–100%) can be manipulated precisely. Ultimately, by introducing this strategy in biological systems, a theoretical torque of more than 76.6 nN·nm (an equivalent force of 85.2 pN) can be exerted in the tumor within 5 minutes, therefore manipulating DNA in cellular systems and in vivo efficiently and opening new avenues for precise nanomedicine in complex biological environments.