Molecular Windows into the Brain: Advances in BBB-Penetrable NIR Fluorescent Imaging Probes

The blood-brain barrier (BBB) is a highly selective permeability barrier that restricts the delivery of diagnostic and therapeutic agents to the brain. Recent advances in near-infrared (NIR) fluorescent probes capable of crossing the BBB have enabled noninvasive in vivo imaging and diagnosis of brain disorders, including depression, epilepsy, stroke, glioma, Alzheimer's disease (AD), and Parkinson's disease (PD). This review highlights the latest developments in the design of BBB-penetrable NIR probes for imaging these neurological conditions. Key design strategies, working mechanisms, and their applications in the detection of disease-specific biomarkers are systematically discussed. Furthermore, current limitations of fluorescent probes are examined along with potential solutions to advance their clinical translation. By providing critical insights into probe development, this review aims to support the creation of NIR probes for early brain disease diagnosis and improved therapeutic interventions.