µ2N-Bots: A Dual-Responsive Cross-Scale Synergistic Strategy for Hierarchical Drug Delivery

Achieving targeted-therapy effects through magnetic micro/nanorobots for drug delivery poses challenges in balancing payload capacity for single-trip transport, stability for long-range delivery, and penetration capability for short-range transport. Here, we propose cross-scale robots, termed µ2N-Bots, with magneto-photothermal responsiveness for on-demand degradation to achieve hierarchical drug delivery. The µ2N-Bots can carry large quantities of magnetic nanorobots (MNRs) and drugs. They can be controllably degraded under near-infrared light or alternating magnetic field stimulation, releasing nanorobots and drugs on demand. Experimental results demonstrate that the µ2N-Bots achieve precise motion under rotationally driven magnetic fields, maintaining stable backward motion or stationary positioning under flow conditions. When encountering impassable barriers, such as narrow passages, the µ2N-Bots degrade near the target area, releasing MNRs that form swarms under rotating magnetic control and migrate deeper. The motion of the swarm formation drives the accumulation of free drugs at the target site, significantly enhancing both the amount and depth of drug delivery. Cell experiments and hemolysis tests validated excellent biocompatibility. This strategy effectively combines the high drug-loading capacity and strong motility of microrobots with the superior penetration capability of nanorobots, offering a novel approach for targeted drug delivery in complex environments.