Nano-imaging agents for brain diseases: Environmentally responsive imaging and therapy

Precise imaging is essential for the accurate diagnosis and surgical guidance of brain diseases but it is challenging due to the difficulties in crossing the blood-brain barrier (BBB), the difficulties in disease lesion targeting, and the limited contrast in the brain environment. Nano-imaging agents were characterized by functionalized modifications, high contrast, small size, and high biocompatibility, thus providing advantages in BBB crossing, brain targeting, imaging resolution, and real-time monitoring, holding great potential in brain disease imaging. Specific characteristics in brain environment and brain diseases (e.g., marker proteins on the BBB, the pathogenic proteins in the neurodegenerative diseases or brain tumors, and the tumor and inflammatory microenvironment) provide opportunities for the functionalized nano-imaging agents to improve BBB crossing and disease targeting. Moreover, the versatile nano-imaging agents are endowed with therapeutic agents to facilitate the theranostics of brain diseases. Here, we summarized the common materials and imaging techniques of nano-imaging agents and their imaging treatment applications. We discussed their BBB penetration, environmental response for disease targeting, and therapeutic effects. We also provided insights on the advantages, challenges, and application of nano-imaging agents in detecting and treating brain diseases such as neurodegenerative diseases, brain tumors, stroke, and traumatic brain injury. These discussions will help develop nano-imaging agents-based theranostic platforms for the precise diagnosis and treatment of brain diseases.