Activatable small-molecule NIR fluorescent/photoacoustic probes for brain disease imaging

초록

NIR small-molecule-based optical imaging has emerged as a cutting-edge tool for probing brain function and pathology with high molecular specificity, real-time visualization, and minimal invasiveness. Among various modalities, fluorescence imaging (FLI) and photoacoustic imaging (PAI) probes have garnered significant attention in brain disease research including Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, and cerebral ischemia due to their complementary strengths in sensitivity, spatial resolution, and penetration depth. We highlighted the design strategies and chemical principles underpinning these imaging agents, followed by detailed discussions of disease biomarker-specific activatable and ratiometric probes. This review further discusses the growing interest in dual-modality FLI/PAI systems, despite current challenges in molecular integration. In summary and outlook, pressing issues are identified such as achieving sufficient blood-brain barrier (BBB) permeability while maintaining optical performance, expanding biomarker responsiveness, and promoting clinical translation through improved pharmacokinetics and human-compatible validation models. This review aims to provide a comprehensive framework for understanding the landscape and future directions of smallmolecule optical imaging probes in neuroscience research and diagnostic innovation.

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