Advances in Nanomedicine for Brain Tumors: Overcoming Biological Barriers, Targeting Strategies, and Future Directions.

PURPOSE OF REVIEW: This review evaluates nanomedicine strategies for brain tumors through a translational lens. Rather than cataloguing nanoparticle formulations, it focuses on representative lipid-based, polymeric, inorganic, self-assembled, protein-based, biomimetic, and nanoconjugate platforms according to the delivery problem they are designed to solve: crossing or bypassing the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), improving intratumoral penetration, controlling payload release, reducing toxicity, or enabling image-guided therapy. RECENT FINDINGS: Preclinical studies show that nanomedicines can increase brain tumor exposure through receptor-mediated transport, physical BBB modulation, local delivery, stimuli-responsive release, biomimetic trafficking, and theranostic integration. However, the strength of evidence remains uneven. Many systems are supported mainly by isolated or model-specific preclinical studies, with limited pharmacokinetic, pharmacodynamic, toxicity, reproducibility, or manufacturing validation. Among clinically tested platforms, gadolinium-based AGuIX nanoparticles currently provide one of the clearest brain tumor-directed examples, supported by early-phase data showing tumor accumulation and acceptable tolerability when combined with radiotherapy. Conversely, the withdrawn SERIL trial of intratumoral JCXH-211 illustrates that mechanistic promise alone does not establish clinical feasibility in glioma. Nanomedicine may improve drug delivery, intratumoral exposure, immunomodulatory payload delivery, and image-guided radiotherapy for brain tumors. Its clinical impact will depend on reproducible central nervous system delivery, validated intratumoral pharmacodynamic readouts, disease-specific safety assessment, scalable good manufacturing practice (GMP)-compliant production, and prospective trials showing benefit over current standards of care.