Abstract
Precision diagnosis and treatment of central nervous system (CNS) diseases are hindered by limited probe penetration, toxicity risks, and low imaging signal-to-noise ratio (SNR). The blood-brain barrier (BBB) further restricts drug delivery, especially in stroke therapy. This study proposes and validates a natural exosome (sExos) from cyanobacteria, featuring intrinsic near-infrared-I (NIR-I) autofluorescence, with strong imaging and neuroprotective functions. As a theranostic nanoplatform, sExos enable integrated diagnosis and treatment of stroke and other brain disorders. Enriched with the fluorescent phycobiliprotein ApcE, sExos support label-free, high-SNR brain imaging in the NIR-I window. In vivo, sExos cross the BBB and accumulate in ischemic lesions, enabling dynamic visualization. Mechanistically, sExos regulate lipid metabolism and inhibit NF-κB signaling, reducing oxidative stress and neuroinflammation, while promoting neural recovery. Toxicity and immunogenicity evaluations confirm excellent biocompatibility and safety. In summary, this naturally autofluorescent exosome offers a label-free, brain-penetrant, and therapeutically promising imaging-intervention strategy, opening avenues for noninvasive stroke therapy and precision CNS disease management.