Transcranial NIR Neuromodulation via Multifunctional Nano‐Optical Electrodes for Relieving Depressive Symptoms

Abstract Neuromodulation stands as a cornerstone in the therapeutic landscape for neurological disorders, yet the quest for selective stimulation of specific brain regions with minimal invasiveness and high spatiotemporal precision remains a formidable challenge. In this study, a multifunctional nano‐optical electrode (NOE) to mitigate depressive symptoms in animal models of depression is introduced. The NOEs' core–shell architecture integrates mesoporous carbon shells for optimal absorption of near‐infrared (NIR) light, alongside superparamagnetic ferric oxide nanocluster cores for magnetic resonance imaging (MRI) visibility. This configuration enables the precise excitation of untransfected neurons using NIR irradiation. The MRI‐guided NIR neuromodulation via NOEs can significantly alleviate depressive symptoms in mice. This is evidenced by the observed enhancement in pleasure‐seeking behaviors, improved motor functions, and a decrease in behaviors indicative of despair. The alleviation of depressive symptoms is ascribed to the NOEs' role as an efficient NIR light transducer, which boosts neuronal activity in the medial prefrontal cortex (mPFC). The MRI compatibility of the NOEs augments the spatial resolution, further refining the precision of neuromodulation. The multimodal, precise, transcranial, and non‐genetic approach of the NOEs‐based neuromodulation strategy heralds a new era in the optical‐theranostics of neurological disorders.