Near-Infrared Neuromodulation: Principles, Nanotechnology-Enabled Platforms, and Emerging Biomedical Frontiers

Optogenetics enables highly specific regulation of neuronal activity with exceptional spatiotemporal precision, providing powerful tools for neural circuit interrogation and the treatment of neurological disorders. However, the limited tissue penetration of visible light restricts its application to deep neural tissues. Near-infrared (NIR) neuromodulation has emerged as a promising alternative by leveraging the superior tissue penetration and minimal invasiveness of NIR light. Recent advances in NIR-responsive nanomaterials, optical engineering, and neurotechnology have rapidly transformed the field from nonspecific photobiomodulation to cell-specific nanotransducer-mediated neuromodulation and integrated neuromodulation systems. In this review, we summarize the optical principles governing NIR propagation in biological tissues and the mechanisms underlying NIR-mediated neural stimulation. We then discuss recent advances in representative NIR nanotransducers, including photothermal, optoelectric, photoacoustic, and NIR-to-visible upconversion platforms together with integrated neuromodulation systems that combine NIR stimulation with multimodal neural recording and closed-loop feedback. We further highlight emerging applications in the central nervous system, optic nerve, and peripheral nerve disorders. Finally, we discuss the key challenges toward clinical translation, including improving tissue penetration, cell specificity, biosafety, and translation, developing intelligent multidisciplinary neuromodulation platforms, and integrating artificial intelligence with closed-loop neural interfaces to achieve adaptive, precise, and personalized neuromodulation.