Biomimetic membrane-coated metal nanoplatforms for enhanced BBB penetration and targeted glioblastoma therapy

Glioblastoma (GBM) is characterized by highly infiltrative growth, pronounced heterogeneity, and adaptive plasticity, leading to poor prognosis and frequent recurrence. Tumor dissemination beyond imaging-defined margins, together with the blood-brain barrier (BBB), heterogeneous blood-brain tumor barrier (BBTB), and immunosuppressive tumor microenvironment, severely limits therapeutic efficacy. Metal-based nanomaterials have emerged as promising theranostic platforms owing to their multifunctionality, enabling multimodal imaging and photothermal, photodynamic, and chemodynamic therapies. However, their clinical translation is constrained by rapid clearance, inadequate BBB/BBTB penetration, and limited intratumoral distribution. Cell membrane-coated metal nanoplatforms have recently emerged as an effective biomimetic strategy to overcome these barriers. By incorporating membranes derived from red blood cells, cancer cells, or immune cells, these systems achieve immune evasion, prolonged circulation, enhanced BBB penetration, and improved tumor targeting. Moreover, recent advances demonstrate their ability to programmably regulate tumor-immune interactions and respond to the tumor microenvironment, shifting nanomedicine from passive delivery toward adaptive theranostic platforms. This review summarizes recent advances in membrane-coated metal nanoplatforms for GBM, highlighting their design principles, biological mechanisms, and applications in synergistic therapy, while discussing their translational potential and the remaining challenges for clinical application.