Polydopamine Nanoparticle‐Mediated Precise Near‐Infrared Optical Stimulation for Cognitive Enhancement

Transcranial neuromodulation faces limitations in precision and depth. This study develops a precise transcranial near-infrared (NIR) neuromodulation technique using polydopamine nanoparticles (PDA NPs) to address cognitive dysfunction. We synthesize 490 nm PDA NPs as photothermal nanomediators for 1064 nm NIR stimulation and assess their mechanisms and effects in PC12 cells and perioperative neurocognitive dysfunction (PND) model mice. In vitro, PDA NP-mediated NIR stimulation exhibits a power-dependent regulatory effect on calcium activity. This activation is mediated through TRPV1, which subsequently enhances mitochondrial membrane potential and intracellular ATP levels. In vivo, this stimulation strategy increases neuronal calcium activity and strengthens gamma oscillations in the hippocampal dentate gyrus (DG). Consequently, the treatment significantly improves spatial memory in both naive and cognitively impaired mice. These findings suggest that PDA NP-mediated NIR neuromodulation offers a promising, precise therapeutic strategy for treating cognitive dysfunction and related neurological disorders.