Recent Advances in Blood-brain Barrier (BBB)-Penetrating Nanomaterials for Neurological Disease Imaging, Diagnosis, and Therapy

The precision diagnosis and effective treatment of neurological diseases have long been hampered by the blood-brain barrier (BBB). Nanomaterials capable of crossing the BBB, endowed with unique advantages such as targeted delivery and transbarrier penetration, provide a crucial solution for overcoming this bottleneck, thereby significantly enhancing the precision and effectiveness of diagnosis and treatment. This review is based on the systematic collection and analysis of recent literature. On this basis, this review summarizes the core characteristics and relative advantages of several major penetration mechanisms: receptor-mediated penetration relies on specific binding to receptors, featuring high targeting specificity and low toxicity; adsorption-mediated penetration depends on surface interactions, with broad universality and simple preparation; and carriermediated penetration achieves transport via carriers, exhibiting high drug-loading capacity but moderate targeting specificity. Correspondingly, different types of nanomaterials have distinct focuses on their applicable scenarios: metallic nanomaterials are suitable for imaging diagnosis, tumor hyperthermia, etc.; polymeric nanomaterials are applicable for drug delivery, gene therapy, etc.; lipid-based nanomaterials are appropriate for small-molecule drug delivery, brain-targeted drug administration, etc. Nanomaterials capable of crossing the BBB share common limitations. For example, these include the long-term biological safety of nanomaterials, challenges in improving targeting efficiency, and hurdles in large-scale preparation. To address the aforementioned limitations, we propose specific and forward-looking future research directions. These include the development of intelligent responsive nanocarriers and the establishment of a standardized toxicity assessment system, which are expected to provide constructive insights for advancing the clinical translation of BBB-crossing nanomaterials in neurological disease diagnosis and treatment.