Local therapeutic platform prevents postsurgical GBM recurrence by diminishing GICs and reshaping immunosuppressive microenvironment

Glioblastoma multiforme (GBM) is characterized by aggressive invasiveness and poor prognosis, and presents a significant clinical challenge due to incomplete surgical resection, poor blood‒brain barrier penetration of therapeutic agents, and inevitable recurrence mainly driven by residual glioma-initiating cells (GICs) and an immunosuppressive microenvironment. Therefore, there is an urgent need to kill remaining GICs and reverse the immunosuppressive tumor microenvironment to prevent postoperative recurrence of GBM. Here, we design an injectable therapeutic platform that targets and kills remaining GICs and reverses the immunosuppressive microenvironment after postoperative resection to prevent the recurrence of GBM. This platform comprises GIC-targeting exosomes that carry siRNA for Notch1 and mitoxantrone to reduce the stemness of GICs and kill residual GICs and glioma cells, respectively, and an immune activator (interleukin-12), which can remodel the immunosuppressive tumor microenvironment, ultimately suppressing postoperative GBM relapse. Our work provides a perspective into the effective inhibition of postresection recurrence of GBM.