In situ formed chemo-immunotherapeutic hydrogel for suppression of postoperative glioma recurrence and intraoperative hemostasis.

Glioma recurrence and intraoperative bleeding present significant challenges in the treatment of glioma. Gliomas are highly invasive and prone to rapid recurrence, while achieving effective hemostasis during neurosurgery remains critical for patient safety and successful outcomes. Here, we present an innovative in-situ formed fibrin gel-based drug delivery system (PX-478 + αPD-1@Gel), co-loaded with PX-478, a selective hypoxia-inducible factor 1α (HIF-1α) inhibitor, and anti-programmed cell death receptor 1 (αPD-1), for controlled and sequential drug release. PX-478 primarily induces apoptosis, arrests the cell cycle, and inhibits the expression of HIF-1α and programmed cell death ligand 1 (PD-L1), thereby alleviating the immunosuppressive tumor microenvironment. This modulation enhances immune T cell infiltration and restores their capacity to eliminate glioma cells. The subsequent release of αPD-1 further amplifies the immune response. This dual intervention significantly suppresses glioma recurrence and prolongs the median survival time in an orthotopic postoperative glioma mouse model. Furthermore, the fibrin gel exhibits rapid coagulation and effective hemostasis, reducing intraoperative bleeding and shortening hemostasis time. This dual-functional system, combining localized chemo-immunotherapy with hemostatic properties, shows substantial promise for improving clinical outcomes in glioma patients.