Time-staggered chemo-immunotherapy via engineered nanofiber resists postoperative dynamic immunosuppression in glioblastoma.

Glioblastoma (GBM) almost inevitably recurs after surgical resection owing to residual infiltrative tumor cells and postoperative immunosuppression. However, delayed initiation of adjuvant therapy fails to restrain rapid tumor regrowth during the early postoperative period. Here, we elucidate postoperative dynamic immune pathology characterized by early explosive tumor proliferation (Ki67⁺ > 38.5%) and progressive protumoral macrophage polarization, and provide a time-staggered chemo-immunotherapy strategy to promptly remedy the postoperative therapeutic gap. To implement the adaptive intervention, we design an engineered nanofiber that enables immediate chemotherapy followed by dynamic immune modulation tailored to the evolving postoperative pathology. Structurally, the tunable nanofiber composition enables time-staggered release of doxorubicin (DOX) to induce immunogenic cell death and BLZ945 to suppress protumoral macrophage programs and abundance. After surgical resection of orthotopic GL261 tumors, a single implantation achieves 83.9% tumor inhibition and establishes immune memory. This study explores the evolving GBM relapse process to guide engineered nanofiber design with time-staggered drug therapy against postoperative recurrence.