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  • Review Article
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Neural modulation with photothermally active nanomaterials

Abstract

Modulating neural electrophysiology with high precision is essential for understanding neural communication and for the diagnosis and treatment of neural disorders. Photothermal modulation offers a remote and non-genetic method for neural modulation with high spatiotemporal resolution and specificity. This technique induces highly localized and transient temperature changes at the cell membrane interfaced with photothermally active nanomaterials. This rapid temperature change affects the electrical properties of the cell membrane or temperature-sensitive ion channels. In this Review, we discuss the fundamental material properties and illumination conditions that are necessary for nanomaterial-assisted photothermal neural excitation and inhibition. We examine how this versatile technique allows direct investigation of neural electrophysiology and signalling pathways in two-dimensional and three-dimensional cell cultures and tissues, and highlight the scientific and technological challenges in terms of cellular specificity, light delivery and biointerface stability on the road to clinical translation.

Key points

  • Nanomaterial-assisted photothermal modulation is a remote, non-genetic technique for the manipulation of neural activity with high spatiotemporal resolution and specificity by inducing a rapid temperature increase at the cell–nanomaterial interface.

  • The fundamental properties of photothermally active nanomaterials (size, dimension, optical absorbance and photothermal energy conversion) and illumination conditions dictate application-specific material selection.

  • Altering light illumination conditions (pulse width, power density and spot size) allows control of neural electrophysiology (excitation and inhibition) and cellular signalling pathways.

  • Evaluation of the cytotoxicity of nanomaterials, phototoxicity of light illumination and local temperature increases is necessary for the safe translation of transient and long-term photothermal modulation.

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Fig. 1: Mechanisms of photothermal modulation.
Fig. 2: Nanomaterial–cell biointerfaces.
Fig. 3: In vitro and in vivo neural excitation with photothermally active nanomaterials.
Fig. 4: Photothermal neural inhibition with nanomaterials.

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Acknowledgements

T.C.-K. acknowledges funding support from the Defense Advanced Research Projects Agency (Award No. D20AC00002) and the National Institute of Health (Award No. R21EB029164).

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Wang, Y., Garg, R., Cohen-Karni, D. et al. Neural modulation with photothermally active nanomaterials. Nat Rev Bioeng 1, 193–207 (2023). https://doi.org/10.1038/s44222-023-00022-y

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