Nanocarriers based therapy and diagnosis of brain diseases: cross the blood-brain barrier

The blood-brain barrier (BBB) is the protective interface that isolates the central nervous system from circulating blood, which restricts approximately 98% of small molecule drugs and nearly all large molecules from entering the brain. Current methods to bypass the BBB, such as laser-guided interstitial thermal therapy and magnetic resonance guided focused ultrasound, are fraught with risks like impairing BBB integrity and brain damage, and are not suitable for long-term treatment. Nanocarriers have emerged as promising tools due to their ability to enhance drug delivery across the BBB while minimizing systemic toxicity. These nanocarriers leverage mechanisms including receptor-mediated, carrier-mediated, cell mediated and extra-stimuli mediated transport to improve BBB traverse and brain targeting. The review evaluates these strategies separately, discussing their potential and limitations for clinical application, and highlights recent advancements in integrating and optimizing nanocarriers utilizing synergistic strategies for the treatment and diagnosis of neurological disorders, including tumors, Alzheimer's disease, Parkinson's disease, and brain infections.