Functional nanomaterial strategies for targeted CNS drug delivery

Effective therapeutic intervention for central nervous system (CNS) diseases, including brain tumors and neurodegenerative disorders, is significantly challenged by the formidable blood-brain barrier (BBB). This biological barrier severely restricts the passage of most drug candidates, resulting in inefficient delivery to pathological sites and substantially contributing to high clinical trial failure rates for CNS therapies. Engineered nanoparticles have emerged as promising functional material systems capable of navigating these delivery obstacles, offering advantages like encapsulating diverse agents, controlled release, and targeted delivery. This review comprehensively analyzes innovative nanoparticle strategies specifically designed to overcome the BBB and achieve precise CNS delivery via systemic administration. We highlight the critical multi-step biological cascade required for successful therapeutic outcomes: maintaining colloidal stability in circulation, efficiently penetrating the BBB, achieving specific accumulation at the disease site, and effectively engaging target cells. Despite significant advancements, clinical translation of these nanoparticle systems remains limited. A thorough understanding of this multi-step process is paramount to accelerating the clinical application of brain-targeted nanomedicines.