Near‐Infrared Fluorescent GABA‐Trp CDs with BBB Penetration for Treatment of Inflammatory Depression

Abstract Carbon dots (CDs) are widely used in biomedical research because of their excellent optical properties and biocompatibility. However, current research often overlooks the physiological activities of CDs, such as their anti‐inflammatory activity, in the nervous system, especially in the brain, resulting in few reports on the utilization of their various properties in disease diagnosis and treatment. Herein, a well‐designed GABA‐tryptophan CDs (GABA‐Trp CDs) with excellent blood–brain barrier (BBB) permeability is prepared through the screening of functional precursors. Exploratory research on its therapeutic effect and corresponding mechanism for inflammatory depressive disorder is conducted based on the verification of its anti‐inflammatory activity. During this process, GABA‐Trp CDs also possess broad‐spectrum emissions, distinguishing them from traditional CDs for deep brain imaging assisted by BBB penetration. The results indicate that GABA‐Trp CDs can treat inflammatory depression through the anti‐inflammatory pathway, including downregulating factors such as lipocalin 2 (Lcn2), and inhibiting the activity of local immune cells in the brain and microglia, further relieving lipid metabolism disorder and repairing myelin damage. The successful application and research of GABA‐Trp CDs in the brain provide new insights into CDs in the field of neurological diagnosis and treatment.