BBB-aware stimuli-responsive and biomimetic nanomedicines for glioblastoma

Glioblastoma (GBM) poses a tremendous challenge because it causes substantial morbidity and mortality. Treatment remains constrained by the tightly regulated blood-brain barrier (BBB) and the heterogeneous blood-brain tumor barrier (BBTB), which together severely limit drug delivery to tumor tissue. Nanomaterial-based drug delivery systems offer an opportunity to overcome the short half-life, low bioavailability, and poor BBB penetration that restrict conventional GBM therapeutics. Nanotechnology also provides safe, effective, and targeted drug delivery systems that enhance penetration, stability, and therapeutic efficacy. This review discusses biomaterials-based nanomedicine platforms for GBM, with a focus on lipid-based carriers, polymeric nanoparticles, dendrimers, inorganic nanomaterials, and biomimetic nanosystems designed to interact with the BBB/BBTB. We summarize how passive and active brain-targeting strategies are combined with endogenous and exogenous stimuli-responsive designs (pH/redox sensitivity, magnetic hyperthermia, photothermal/photodynamic therapy, and ultrasound-triggered systems) to enhance intratumoral accumulation and anti-GBM efficacy. Overall, this review discusses recent advances in BBB-aware, stimuli-responsive, and biomimetic nanomedicines for GBM, and outlines their therapeutic potential alongside persistent challenges in safety, large-scale manufacturing, and clinical translation.