Graphdiyne as a Highly Efficient and Neuron-Targeted Photothermal Transducer for <i>in Vivo</i> Neuromodulation.

Abstract

Photothermal modulation of neural activity offers a promising approach for understanding brain circuits and developing therapies for neurological disorders. However, the low neuron selectivity and inefficient light-to-heat conversion of existing photothermal nanomaterials significantly limit their potential for neuromodulation. Here, we report that graphdiyne (GDY) can be developed into an efficient neuron-targeted photothermal transducer for <i>in vivo</i> modulation of neuronal activity through rational surface functionalization. We functionalize GDY with polyethylene glycol (PEG) through noncovalent hydrophobic interactions, followed by antibody conjugation to specifically target the temperature-sensitive transient receptor potential cation channel subfamily V member 1 (TRPV1) on the surface of neural cells. The nanotransducer not only exhibits high photothermal conversion efficiency in the near-infrared region but also shows great TRPV1-targeting capability. This enables photothermal activation of TRPV1, leading to neurotransmitter release in cells and modulation of neural firing in living mice. With its precision and selectivity, the GDY-based transducer provides an innovative avenue for understanding brain function and developing therapeutic strategies for neurodegenerative diseases.