Autologous Nanovaccine Induces Immunogenic Domino Effect to Prevent Postoperative Recurrence of Orthotopic Glioblastoma

Abstract Glioblastoma (GBM), the most aggressive form of primary intracranial tumors, poses significant challenges for effective treatment. The highly invasive characteristics of GBM render complete tumor resection exceedingly difficult and frequently lead to postoperative recurrence. To address this issue, a novel autologous nano vaccine is developed to convert the immunosuppressive microenvironment into an active immune landscape through an immunogenic domino effect, thereby targeting residual tumor cells and preventing GBM recurrence. This nanovaccine is formulated by co‐loading lipopolysaccharide (LPS) and glioblastoma cell lysates (GCL) into layered double hydroxide (LDH) nanosheets, which are subsequently integrated within an injectable alginate hydrogel to create LLGA‐Gel. The nanovaccine exploits the immunogenic potential of GCL in conjunction with the immunostimulatory properties of LPS to induce pyroptotic cell death, enhance dendritic cell maturation, and promote macrophage polarization toward an M1 phenotype; these effects culminate in increased CD8 ⁺ T cell infiltration and reduced Foxp3 ⁺ Tregs at the tumor site. In vivo experiments demonstrate that this nanovaccine not only enhances the efficacy of immunogenic cell death but also significantly amplifies the immune response, thereby markedly reducing the postoperative recurrence of orthotopic GBM. This study underscores the promise of nanotechnology‐enhanced immunotherapy in developing effective nanovaccines against GBM.