Adaptive intrathecal nanorobotics in mice and nonhuman primates for navigated CNS therapy

Intrathecal delivery for central nervous system (CNS) therapy lacks spatiotemporal control due to spinal canal anatomical constraints, especially at human scale. We developed an adaptive magnetic nanorobotic platform enabling multimode swarm mobility for in vivo spinal canal navigation in mice and nonhuman primates. Programmable chain-like, vortex-like, and ribbon-like swarm were accomplished, and vortex swarm was indicated as optimal strategy for adaptive intrathecal navigation. Driven by a robotic arm-generated magnetic field, the vortex swarms indicate navigation within spinal canal over centimeter distances, which magnetically enhanced accumulation at CNS target sites and prolonged their in vivo retention, thereby substantially enhancing their therapeutic efficacy compared with conventional passive intravascular delivery, with minimal side effects. Tests in nonhuman primates indicate that the nanorobotic swarm migration is from the gap between the bundles of cauda equina and then the spin cord, revealing their morphological adaption at the cauda equina interface to circumvent anatomical constraints.