Potassium-scavenging train-style nanorobots potentiate radiotherapy and reverse immunosuppression in glioblastoma

Radiotherapy (RT) is essential for glioblastoma treatment but is compromised by two key challenges: hypoxic radio-resistance and the post-radiotherapy leakage of intracellular potassium ions (K + ) that creates a profound immunosuppressive microenvironment, impairing T cell function and driving macrophage M2 polarization. While existing strategies largely focus on radiosensitizers to overcome hypoxia, few address the downstream consequence of K + -mediated immunosuppression. Herein, we engineer a train-style nanorobot (M@Ang-SiO 2 –Au–Pd) that concurrently overcomes both obstacles. The nanorobot features an angiopep-2-modified SiO 2 head for targeted glioblastoma delivery and an asymmetric Pd tail with catalase-like and peroxidase-like nanozyme activities. At the tumor site, Pd catalyzes H 2 O 2 conversion into O 2 to provide bubble propulsion for deep penetration, while Au–Pd amplify X-ray energy deposition and generate lethal hydroxyl radicals (·OH) to synergistically enhance radiotherapy-induced apoptosis. The nanorobot is coated with a K⁺-selective membrane (M). This design enables its SiO₂ head to specifically capture K⁺ leaked from dying tumor cells. By maintaining low intratumoral K⁺ levels, it prevents macrophages from adopting the immunosuppressive M2 phenotype and alleviates T cell exhaustion. Together, these effects effectively reverse tumor immunosuppression. In an orthotopic glioblastoma model, the nanorobot demonstrated precise tumor targeting, enhanced radio-sensitization, and potent K⁺ regulation. This combination triggered a robust antitumor immune response and significantly prolonged survival. This work establishes a novel paradigm employing nanorobots as ion-adsorbing carriers to modulate the post-radiotherapy ionic microenvironment for synergistic therapy.