Dual-Responsive Nanorobot-Based Marsupial Robotic System for Intracranial Cross-Scale Targeting Drug Delivery

Nanorobots capable of active movement are an exciting technology for targeted therapeutic intervention. However, the extensive motion range and hindrance of the blood-brain barrier impeded their clinical translation in glioblastoma therapy. Here, a marsupial robotic system constructed by integrating chemical/magnetic hybrid nanorobots (child robots) with a miniature magnetic continuum robot (mother robot) for intracranial cross-scale targeting drug delivery is reported. For primary targeting on macroscale, the continuum robot enters the cranial cavity through a minimally invasive channel (e.g., Ommaya device) in the skull and transports the nanorobots to pathogenic regions. Upon circumventing the blood-brain barrier, the released nanorobots perform secondary targeting on microscale to further enhance the spatial resolution of drug delivery. In vitro experiments against primary glioblastoma cells derived from different patients are conducted for personalized treatment guidance. The operation feasibility within organisms is shown in ex vivo swine brain experiments. The biosafety of the treatment system is suggested in in vivo experiments. Owing to the hierarchical targeting method, the targeting rate, targeting accuracy, and treatment efficacy have improved greatly. The marsupial robotic system offers a novel intracranial local therapeutic strategy and constitutes a key milestone in the development of glioblastoma treatment platforms.