mRNA vaccines for glioblastoma: integrating multiomics and nanomedicine to overcome spatiotemporal heterogeneity.

Glioblastoma (GBM) remains among the most lethal central nervous system (CNS) malignancies, characterized by inevitable recurrence and dismal prognosis. GBM exhibits profound spatiotemporal heterogeneity, continuously evading the immune system and developing drug resistance, which results in limited efficacy of traditional therapies. In this context, mRNA vaccines have emerged as a programmable immunotherapeutic platform well-suited to address this dynamic challenge. Recent advances in multiomics technologies enable systematic identification and real-time tracking of tumor-specific antigens, providing a dynamic roadmap of the evolving tumor ecosystem. Concurrently, engineered nanoparticle delivery systems demonstrate the capacity to navigate the sequential spatial barriers constraining GBM therapy. The integration of multiomics-guided mRNA vaccine design with precision nanocarriers represents a transformative strategy for achieving spatiotemporally matched immunotherapy. This review examines how multiomics approaches enable dynamic antigen discovery, analyzes the mechanisms by which mRNA vaccines activate CNS immunity, evaluates nanoparticle platforms designed to overcome biological barriers, and discusses emerging strategies for spatiotemporally coordinated combination therapies and clinical translation. Ultimately, we propose a paradigm of spatiotemporally matched therapy that integrates multiomics sensing, mRNA programmability, and nanomedicine precision to address the dynamic challenges in GBM.