Reader TTS

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. Access through your institution

Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 digital issues and

online access to articles $119.00 per year only $9.92 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to

local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT

BEING VIEWED BY OTHERS NON-GENETIC PHOTOACOUSTIC STIMULATION OF SINGLE NEURONS BY A TAPERED FIBER OPTOACOUSTIC EMITTER Article Open access 14 July 2021 INFRARED NEURAL STIMULATION AND

INHIBITION USING AN IMPLANTABLE SILICON PHOTONIC MICRODEVICE Article Open access 01 June 2020 TETHER-FREE PHOTOTHERMAL DEEP-BRAIN STIMULATION IN FREELY BEHAVING MICE VIA WIDE-FIELD

ILLUMINATION IN THE NEAR-INFRARED-II WINDOW Article 21 March 2022 REFERENCES * Liang, E., Shi, J. & Tian, B. Freestanding nanomaterials for subcellular neuronal interfaces. _iScience_

25, 103534 (2022). Article  Google Scholar  * Hong, J.-w, Yoon, C., Jo, K., Won, J. H. & Park, S. Recent advances in recording and modulation technologies for next-generation neural

interfaces. _iScience_ 24, 103550 (2021). Article  Google Scholar  * Kang, S.-K., Koo, J., Lee, Y. K. & Rogers, J. A. Advanced materials and devices for bioresorbable electronics. _Acc.

Chem. Res._ 51, 988–998 (2018). Article  Google Scholar  * Rogers, J. A., Someya, T. & Huang, Y. Materials and mechanics for stretchable electronics. _Science_ 327, 1603–1607 (2010).

Article  Google Scholar  * Song, E., Li, J., Won, S. M., Bai, W. & Rogers, J. A. Materials for flexible bioelectronic systems as chronic neural interfaces. _Nat. Mater._ 19, 590–603

(2020). Article  Google Scholar  * Hong, G. & Lieber, C. M. Novel electrode technologies for neural recordings. _Nat. Rev. Neurosci._ 20, 330–345 (2019). Article  Google Scholar  *

Zhang, A. & Lieber, C. M. Nano-bioelectronics. _Chem. Rev._ 116, 215–257 (2016). Article  Google Scholar  * Balakrishnan, G., Song, J., Mou, C. & Bettinger, C. J. Recent progress in

materials chemistry to advance flexible bioelectronics in medicine. _Adv. Mater._ 34, 2106787 (2022). Article  Google Scholar  * Garg, R., Roman, D. S., Wang, Y., Cohen-Karni, D. &

Cohen-Karni, T. Graphene nanostructures for input–output bioelectronics. _Biophys. Rev._ 2, 041304 (2021). Article  Google Scholar  * Bergman, H., Wichmann, T. & DeLong, M. R. Reversal

of experimental parkinsonism by lesions of the subthalamic nucleus. _Science_ 249, 1436–1438 (1990). Article  Google Scholar  * Spira, M. E. & Hai, A. Multi-electrode array technologies

for neuroscience and cardiology. _Nat. Nanotechnol._ 8, 83–94 (2013). Article  Google Scholar  * Engel, A. K., Moll, C. K., Fried, I. & Ojemann, G. A. Invasive recordings from the human

brain: clinical insights and beyond. _Nat. Rev. Neurosci._ 6, 35–47 (2005). Article  Google Scholar  * Polikov, V. S., Tresco, P. A. & Reichert, W. M. Response of brain tissue to

chronically implanted neural electrodes. _J. Neurosci. Methods_ 148, 1–18 (2005). Article  Google Scholar  * Rivnay, J., Wang, H., Fenno, L., Deisseroth, K. & Malliaras, G. G.

Next-generation probes, particles, and proteins for neural interfacing. _Sci. Adv._ 3, e1601649 (2017). Article  Google Scholar  * Gulino, M., Kim, D., Pané, S., Santos, S. D. & Pêgo, A.

P. Tissue response to neural implants: the use of model systems toward new design solutions of implantable microelectrodes. _Front. Neurosci._ 13, 689 (2019). Article  Google Scholar  *

Carnicer-Lombarte, A., Chen, S.-T., Malliaras, G. G. & Barone, D. G. Foreign body reaction to implanted biomaterials and its impact in nerve neuroprosthetics. _Front. Bioeng.

Biotechnol._ 9, 622524 (2021). Article  Google Scholar  * Salatino, J. W., Ludwig, K. A., Kozai, T. D. & Purcell, E. K. Glial responses to implanted electrodes in the brain. _Nat.

Biomed. Eng._ 1, 862–877 (2017). Article  Google Scholar  * Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Millisecond-timescale, genetically targeted optical control

of neural activity. _Nat. Neurosci._ 8, 1263–1268 (2005). Article  Google Scholar  * Sahel, J.-A. et al. Partial recovery of visual function in a blind patient after optogenetic therapy.

_Nat. Med._ 27, 1223–1229 (2021). Article  Google Scholar  * Chernov, M. & Roe, A. W. Infrared neural stimulation: a new stimulation tool for central nervous system applications.

_Neurophotonics_ 1, 011011 (2014). Article  Google Scholar  * Packer, A. M., Roska, B. & Häusser, M. Targeting neurons and photons for optogenetics. _Nat. Neurosci._ 16, 805–815 (2013).

Article  Google Scholar  * Plaksin, M., Shapira, E., Kimmel, E. & Shoham, S. Thermal transients excite neurons through universal intramembrane mechanoelectrical effects. _Phys. Rev. X_

8, 011043 (2018). Google Scholar  * Wells, J. et al. Optical stimulation of neural tissue in vivo. _Opt. Lett._ 30, 504–506 (2005). Article  Google Scholar  * Wells, J. D., Kao, C., Jansen,

E. D., Konrad, P. E. & Mahadevan-Jansen, A. Application of infrared light for in vivo neural stimulation. _J. Biomed. Opt._ 10, 064003 (2005). Article  Google Scholar  * Jenkins, M. W.

et al. Optical pacing of the embryonic heart. _Nat. Photonics_ 4, 623–626 (2010). Article  Google Scholar  * Liljemalm, R., Nyberg, T. & von Holst, H. Heating during infrared neural

stimulation. _Lasers Surg. Med._ 45, 469–481 (2013). Article  Google Scholar  * Wells, J. D. et al. Optically mediated nerve stimulation: Identification of injury thresholds. _Lasers Surg.

Med._ 39, 513–526 (2007). Article  Google Scholar  * Zimmerman, J. F. & Tian, B. Nongenetic optical methods for measuring and modulating neuronal response. _ACS Nano_ 12, 4086–4095

(2018). Article  Google Scholar  * Rastogi, S. K. et al. Remote nongenetic optical modulation of neuronal activity using fuzzy graphene. _Proc. Natl Acad. Sci. USA_ 117, 13339–13349 (2020).

THIS ARTICLE REPORTS TEMPLATED GRAPHENE NANOSTRUCTURES THAT ENABLE REMOTE, NON-GENETIC PHOTOTHERMAL STIMULATION WITH LASER ENERGIES AS LOW AS SUB-HUNDRED NANOJOULES WITHOUT GENERATING

CELLULAR STRESS. Article  Google Scholar  * Chen, R., Romero, G., Christiansen, M. G., Mohr, A. & Anikeeva, P. Wireless magnetothermal deep brain stimulation. _Science_ 347, 1477–1480

(2015). Article  Google Scholar  * Fang, Y. et al. Texturing silicon nanowires for highly localized optical modulation of cellular dynamics. _Nano Lett._ 18, 4487–4492 (2018). Article 

Google Scholar  * Sebesta, C. et al. Subsecond multichannel magnetic control of select neural circuits in freely moving flies. _Nat. Mater._ 21, 951–958 (2022). Article  Google Scholar  *

Duret, G. et al. Magnetic entropy as a proposed gating mechanism for magnetogenetic ion channels. _Biophys. J._ 116, 454–468 (2019). Article  Google Scholar  * Jiang, Y. & Tian, B.

Inorganic semiconductor biointerfaces. _Nat. Rev. Mater._ 3, 473–490 (2018). Article  Google Scholar  * Ghezzi, D. et al. A hybrid bioorganic interface for neuronal photoactivation. _Nat.

Commun._ 2, 166 (2011). THIS ARTICLE PRESENTS PHOTOTHERMAL EXCITATION OF PRIMARY NEURONS USING SHORT PULSES OF VISIBLE LIGHT AT THE INTERFACED ORGANIC THIN FILMS. Article  Google Scholar  *

Bareket-Keren, L. & Hanein, Y. Novel interfaces for light directed neuronal stimulation: advances and challenges. _Int. J. Nanomed._ 9, 65 (2014). Article  Google Scholar  * Jiang, Y. et

al. Rational design of silicon structures for optically controlled multiscale biointerfaces. _Nat. Biomed. Eng._ 2, 508–521 (2018). Article  Google Scholar  * Ye, E. & Li, Z.

_Photothermal Nanomaterials_. Vol. 54 (Royal Society of Chemistry, 2022). * Carvalho-de-Souza, J. L. et al. Photosensitivity of neurons enabled by cell-targeted gold nanoparticles. _Neuron_

86, 207–217 (2015). Article  Google Scholar  * Wang, Y. et al. Ti3C2Tx MXene flakes for optical control of neuronal electrical activity. _ACS Nano_ 15, 14662–14671 (2021). THE ARTICLE

REPORTS 2D MXENE FILMS AND FLAKES THAT ENABLE SUBCELLULAR PHOTOTHERMAL STIMULATION WITH ENERGIES AS LOW AS TENS OF MICROJOULES PER PULSE. Article  Google Scholar  * Lyu, Y., Xie, C.,

Chechetka, S. A., Miyako, E. & Pu, K. Semiconducting polymer nanobioconjugates for targeted photothermal activation of neurons. _J. Am. Chem. Soc._ 138, 9049–9052 (2016). Article  Google

Scholar  * Carvalho-de-Souza, J. L., Pinto, B. I., Pepperberg, D. R. & Bezanilla, F. Optocapacitive generation of action potentials by microsecond laser pulses of nanojoule energy.

_Biophys. J._ 114, 283–288 (2018). Article  Google Scholar  * Pinto, B. I., Bassetto, C. A. & Bezanilla, F. Optocapacitance: physical basis and its application. _Biophys. Rev._ 14,

569–577 (2022). THIS ARTICLE EXPLAINS THE THEORETICAL BASIS OF OPTOCAPACITIVE-BASED PHOTOTHERMAL EXCITATION. Article  Google Scholar  * Jung, S. et al. Photothermal response induced by

nanocage-coated artificial extracellular matrix promotes neural stem cell differentiation. _Nanomaterials_ 11, 1216 (2021). Article  Google Scholar  * Paviolo, C. et al. Laser exposure of

gold nanorods can increase neuronal cell outgrowth. _Biotechnol. Bioeng._ 110, 2277–2291 (2013). Article  Google Scholar  * Masini, D. & Kiehn, O. Targeted activation of midbrain neurons

restores locomotor function in mouse models of parkinsonism. _Nat. Commun._ 13, 504 (2022). Article  Google Scholar  * Zhang, Y. et al. Targeting thalamic circuits rescues motor and mood

deficits in PD mice. _Nature_ 607, 321–329 (2022). Article  Google Scholar  * Li, M. C. & Cook, M. J. Deep brain stimulation for drug-resistant epilepsy. _Epilepsia_ 59, 273–290 (2018).

Article  Google Scholar  * Hodgkin, A. L. & Huxley, A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. _J. Physiol._ 117,

500–544 (1952). Article  Google Scholar  * Manfredi, G. et al. The physics of plasma membrane photostimulation. _APL Mater._ 9, 030901 (2021). THIS ARTICLE DESCRIBES THE PHYSICAL PHENOMENA

RESPONSIBLE FOR PHOTOSTIMULATION USING THE SIMPLE EQUIVALENT CIRCUIT MODEL OF THE CELL MEMBRANE. Article  Google Scholar  * Eom, K., Byun, K. M., Jun, S. B., Kim, S. J. & Lee, J.

Theoretical study on gold-nanorod-enhanced near-infrared neural stimulation. _Biophys. J._ 115, 1481–1497 (2018). Article  Google Scholar  * Martino, N. et al. Photothermal cellular

stimulation in functional bio-polymer interfaces. _Sci. Rep._ 5, 8911 (2015). Article  Google Scholar  * Wu, X. et al. Tether-free photothermal deep-brain stimulation in freely behaving mice

via wide-field illumination in the near-infrared-II window. _Nat. Biomed. Eng._ 6, 754–770 (2022). THIS ARTICLE DEMONSTRATES IN VIVO PHOTOTHERMAL STIMULATION OF TRPV1-EXPRESSING NEURONS

USING NIR-II RESPONSIVE MACROMOLECULAR TRANSDUCTORS. Article  Google Scholar  * Gribi, S., du Bois de Dunilac, S., Ghezzi, D. & Lacour, S. P. A microfabricated nerve-on-a-chip platform

for rapid assessment of neural conduction in explanted peripheral nerve fibers. _Nat. Commun._ 9, 4403 (2018). Article  Google Scholar  * Patapoutian, A., Peier, A. M., Story, G. M. &

Viswanath, V. ThermoTRP channels and beyond: mechanisms of temperature sensation. _Nat. Rev. Neurosci._ 4, 529–539 (2003). Article  Google Scholar  * Ramos, A. P., Cruz, M. A., Tovani, C. B.

& Ciancaglini, P. Biomedical applications of nanotechnology. _Biophys. Rev._ 9, 79–89 (2017). Article  Google Scholar  * McNamara, K. & Tofail, S. A. Nanoparticles in biomedical

applications. _Adv. Phys. X_ 2, 54–88 (2017). Google Scholar  * Vajtai, R. _Springer Handbook of Nanomaterials_ (Springer Science & Business Media, 2013). * Wang, Y. & Guo, L.

Nanomaterial-enabled neural stimulation. _Front. Neurosci._ 10, 69 (2016). Article  Google Scholar  * Dykman, L. & Khlebtsov, N. Gold nanoparticles in biology and medicine: recent

advances and prospects. _Acta Naturae_ 3, 34–55 (2011). Article  Google Scholar  * Giljohann, D. A. et al. In _Spherical Nucleic Acids_, 55–90 (Jenny Stanford Publishing, 2020). * Roper, D.

K., Ahn, W. & Hoepfner, M. Microscale heat transfer transduced by surface plasmon resonant gold nanoparticles. _J. Phys. Chem. C._ 111, 3636–3641 (2007). Article  Google Scholar  * Bera,

D., Qian, L., Tseng, T.-K. & Holloway, P. H. Quantum dots and their multimodal applications: a review. _Materials_ 3, 2260–2345 (2010). Article  Google Scholar  * Altavilla, C. &

Ciliberto, E. _Inorganic Nanoparticles: Synthesis, Applications, and Perspectives_ (CRC Press, 2017). * Rao, J. P. & Geckeler, K. E. Polymer nanoparticles: preparation techniques and

size-control parameters. _Prog. Polym. Sci._ 36, 887–913 (2011). Article  Google Scholar  * Zielińska, A. et al. Polymeric nanoparticles: production, characterization, toxicology and

ecotoxicology. _Molecules_ 25, 3731 (2020). Article  Google Scholar  * Gholami Derami, H. et al. Reversible photothermal modulation of electrical activity of excitable cells using

polydopamine nanoparticles. _Adv. Mater._ 33, 2008809 (2021). Article  Google Scholar  * Yan, R., Gargas, D. & Yang, P. Nanowire photonics. _Nat. Photonics_ 3, 569–576 (2009). Article 

Google Scholar  * Shi, J., Sun, C., Liang, E. & Tian, B. Semiconductor nanowire-based cellular and subcellular interfaces. _Adv. Funct. Mater._ 32, 2107997 (2021). Article  Google

Scholar  * Tian, B. et al. Three-dimensional, flexible nanoscale field-effect transistors as localized bioprobes. _Science_ 329, 830–834 (2010). Article  Google Scholar  * Zhou, W., Dai, X.

& Lieber, C. M. Advances in nanowire bioelectronics. _Rep. Prog. Phys._ 80, 016701 (2016). Article  Google Scholar  * Wagner, A. R. & Ellis, S. W. Vapor-liquid-solid mechanism of

single crystal growth. _Appl. Phys. Lett._ 4, 89–90 (1964). Article  Google Scholar  * Schmidt, V., Wittemann, J. & Gosele, U. Growth, thermodynamics, and electrical properties of

silicon nanowires. _Chem. Rev._ 110, 361–388 (2010). Article  Google Scholar  * Tian, B. et al. Coaxial silicon nanowires as solar cells and nanoelectronic power sources. _Nature_ 449,

885–889 (2007). Article  Google Scholar  * VahidMohammadi, A., Rosen, J. & Gogotsi, Y. The world of two-dimensional carbides and nitrides (MXenes). _Science_ 372, eabf1581 (2021).

Article  Google Scholar  * Naguib, M. et al. Two-dimensional nanocrystals produced by exfoliation of Ti3AlC2. _Adv. Mater._ 23, 4248–4253 (2011). Article  Google Scholar  * Gogotsi, Y. &

Huang, Q. MXenes: two-dimensional building blocks for future materials and devices. _ACS Nano_ 15, 5775–5780 (2021). Article  Google Scholar  * Gao, P. et al. Biomedical applications of 2D

monoelemental materials formed by group VA and VIA: a concise review. _J. Nanobiotechnol._ 19, 96 (2021). Article  Google Scholar  * Driscoll, N. et al. Two-dimensional Ti3C2 MXene for

high-resolution neural interfaces. _ACS Nano_ 12, 10419–10429 (2018). Article  Google Scholar  * Lin, H., Wang, X., Yu, L., Chen, Y. & Shi, J. Two-dimensional ultrathin MXene ceramic

nanosheets for photothermal conversion. _Nano Lett._ 17, 384–391 (2017). Article  Google Scholar  * Driscoll, N. et al. MXene-infused bioelectronic interfaces for multiscale

electrophysiology and stimulation. _Sci. Transl. Med._ 13, eabf8629 (2021). Article  Google Scholar  * Hantanasirisakul, K. & Gogotsi, Y. Electronic and optical properties of 2D

transition metal carbides and nitrides (MXenes). _Adv. Mater._ 30, 1804779 (2018). Article  Google Scholar  * Yaroslavsky, A. N. et al. Optical properties of selected native and coagulated

human brain tissues in vitro in the visible and near infrared spectral range. _Phys. Med. Biol._ 47, 2059–2073 (2002). Article  Google Scholar  * Shuck, C. E. et al. Scalable synthesis of

Ti3C2T_x_ MXene. _Adv. Eng. Mater._ 22, 1901241 (2020). Article  Google Scholar  * San Roman, D., Garg, R. & Cohen-Karni, T. Bioelectronics with graphene nanostructures. _APL Mater._ 8,

100906 (2020). Article  Google Scholar  * Garg, R. et al. Nanowire-mesh-templated growth of out-of-plane three-dimensional fuzzy graphene. _ACS Nano_ 11, 6301–6311 (2017). Article  Google

Scholar  * Garg, R. et al. Electron transport in multidimensional fuzzy graphene nanostructures. _Nano Lett._ 19, 5335–5339 (2019). Article  Google Scholar  * San Roman, D. et al.

Engineering three-dimensional (3D) out-of-plane graphene edge sites for highly selective two-electron oxygen reduction electrocatalysis. _ACS Catal._ 10, 1993–2008 (2020). Article  Google

Scholar  * Rastogi, S. K. et al. Three-dimensional fuzzy graphene ultra-microelectrodes for subcellular electrical recordings. _Nano Res._ 13, 1444–1452 (2020). Article  Google Scholar  *

Gong, W. et al. Thermal transport in multidimensional silicon-graphene hybrid nanostructures. _ACS Appl. Mater. Interfaces_ 13, 50206–50212 (2021). Article  Google Scholar  * Huang, X. &

El-Sayed, M. A. Gold nanoparticles: Optical properties and implementations in cancer diagnosis and photothermal therapy. _J. Adv. Res._ 1, 13–28 (2010). Article  Google Scholar  * Mie, G.

Contributions to the optics of turbid media, particularly of colloidal metal solutions. _Ann. Phys._ 25, 377–445 (1976). Google Scholar  * Papavassiliou, G. C. Optical properties of small

inorganic and organic metal particles. _Prog. Solid. State Chem._ 12, 185–271 (1979). Article  Google Scholar  * Link, S. & El-Sayed, M. A. Size and temperature dependence of the plasmon

absorption of colloidal gold nanoparticles. _J. Phys. Chem. B_ 103, 4212–4217 (1999). Article  Google Scholar  * Chen, H. et al. Understanding the photothermal conversion efficiency of gold

nanocrystals. _Small_ 6, 2272–2280 (2010). Article  Google Scholar  * Lee, K.-S. & El-Sayed, M. A. Dependence of the enhanced optical scattering efficiency relative to that of

absorption for gold metal nanorods on aspect ratio, size, end-cap shape, and medium refractive index. _J. Phys. Chem. B_ 109, 20331–20338 (2005). Article  Google Scholar  * Anayee, M. et al.

Role of acid mixtures etching on the surface chemistry and sodium ion storage in Ti3C2Tx MXene. _Chem. Commun._ 56, 6090–6093 (2020). Article  Google Scholar  * Maleski, K., Shuck, C. E.,

Fafarman, A. T. & Gogotsi, Y. The broad chromatic range of two-dimensional transition metal carbides. _Adv. Opt. Mater._ 9, 2001563 (2021). Article  Google Scholar  * Lin, H. et al. A

90-nm-thick graphene metamaterial for strong and extremely broadband absorption of unpolarized light. _Nat. Photonics_ 13, 270–276 (2019). Article  Google Scholar  * Campbell, P. &

Green, M. A. Light trapping properties of pyramidally textured surfaces. _J. Appl. Phys._ 62, 243–249 (1987). Article  Google Scholar  * Yablonovitch, E. Statistical ray optics. _J. Opt.

Soc. Am._ 72, 899–907 (1982). Article  Google Scholar  * Dipalo, M. et al. Intracellular action potential recordings from cardiomyocytes by ultrafast pulsed laser irradiation of fuzzy

graphene microelectrodes. _Sci. Adv._ 7, eabd5175 (2021). Article  Google Scholar  * Yong, J. et al. Gold-nanorod-assisted near-infrared stimulation of primary auditory neurons. _Adv.

Healthc. Mater._ 3, 1862–1868 (2014). Article  Google Scholar  * Jiang, Y. et al. Nongenetic optical neuromodulation with silicon-based materials. _Nat. Protoc._ 14, 1339–1376 (2019). THE

ARTICLE PRESENTS A DETAILED PROTOCOL FOR THE CHARACTERIZATION OF THE LOCAL TEMPERATURE RESPONSE OF NANOMATERIALS USING MICRO-PIPETTE AND NANO-PIPETTE THERMOMETRY. Article  Google Scholar  *

Tobías, I., Cañizo, C. D. & Alonso, J. In _Handbook of Photovoltaic Science and Engineering_ 255–306 (Wiley, 2003). * Walter, M. G. et al. Solar water splitting cells. _Chem. Rev._ 110,

6446–6473 (2010). Article  Google Scholar  * Su, Y. et al. Gold nanoparticles-decorated silicon nanowires as highly efficient near-infrared hyperthermia agents for cancer cells destruction.

_Nano Lett._ 12, 1845–1850 (2012). Article  Google Scholar  * Gao, M., Zhu, L., Peh, C. K. & Ho, G. W. Solar absorber material and system designs for photothermal water vaporization

towards clean water and energy production. _Energy Environ. Sci._ 12, 841–864 (2019). Article  Google Scholar  * Hao, J. et al. High performance optical absorber based on a plasmonic

metamaterial. _Appl. Phys. Lett._ 96, 251104 (2010). Article  Google Scholar  * Li, R., Zhang, L., Shi, L. & Wang, P. MXene Ti3C2: an effective 2D light-to-heat conversion material. _ACS

Nano_ 11, 3752–3759 (2017). Article  Google Scholar  * Lee, U., Yoo, C.-J., Kim, Y.-J. & Yoo, Y.-M. Cytotoxicity of gold nanoparticles in human neural precursor cells and rat cerebral

cortex. _J. Biosci. Bioeng._ 121, 341–344 (2016). Article  Google Scholar  * Sani, A., Cao, C. & Cui, D. Toxicity of gold nanoparticles (AuNPs): a review. _Biochem. Biophys. Rep._ 26,

100991 (2021). Google Scholar  * Eom, K. et al. Enhanced infrared neural stimulation using localized surface plasmon resonance of gold nanorods. _Small_ 10, 3853–3857 (2014). THIS ARTICLE

DEMONSTRATES PHOTOTHERMAL EXCITATION OF THE SCIATIC NERVE USING PULSED INFRARED ILLUMINATION OF INTERFACED PLASMONIC GOLD NANORODS. Article  Google Scholar  * Lewinski, N., Colvin, V. &

Drezek, R. Cytotoxicity of nanoparticles. _Small_ 4, 26–49 (2008). Article  Google Scholar  * Tosheva, K. L., Yuan, Y., Pereira, P. M., Culley, S. & Henriques, R. Between life and death:

strategies to reduce phototoxicity in super-resolution microscopy. _J. Phys. D Appl. Phys._ 53, 163001 (2020). Article  Google Scholar  * Stockley, J. H. et al. Surpassing light-induced

cell damage in vitro with novel cell culture media. _Sci. Rep._ 7, 849 (2017). Article  Google Scholar  * Kuse, Y., Ogawa, K., Tsuruma, K., Shimazawa, M. & Hara, H. Damage of

photoreceptor-derived cells in culture induced by light emitting diode-derived blue light. _Sci. Rep._ 4, 5223 (2014). Article  Google Scholar  * Lim, G. P. et al. Cytotoxicity of

MXene-based nanomaterials for biomedical applications: a mini review. _Environ. Res._ 201, 111592 (2021). Article  Google Scholar  * Matino, L., Rastogi, S. K., Garma, L. D., Cohen-Karni, T.

& Santoro, F. Characterization of the coupling between out-of-plane graphene and electrogenic cells. _Adv. Mater. Interfaces_ 7, 2000699 (2020). Article  Google Scholar  * Mullick

Chowdhury, S. et al. Cell specific cytotoxicity and uptake of graphene nanoribbons. _Biomaterials_ 34, 283–293 (2013). Article  Google Scholar  * Li, Z. et al. Cellular level

biocompatibility and biosafety of ZnO nanowires. _J. Phys. Chem. C._ 112, 20114–20117 (2008). Article  Google Scholar  * Jastrzębska, A. et al. In vitro studies on cytotoxicity of

delaminated Ti3C2 MXene. _J. Hazard. Mater._ 339, 1–8 (2017). Article  Google Scholar  * Dai, C. et al. Biocompatible 2D titanium carbide (MXenes) composite nanosheets for pH-responsive

MRI-guided tumor hyperthermia. _Chem. Mater._ 29, 8637–8652 (2017). Article  Google Scholar  * Zhang, L. et al. Mechanisms of reactive oxygen species generated by inorganic nanomaterials for

cancer therapeutics. _Front. Chem._ 9, 630969 (2021). Article  Google Scholar  * Bergamini, C. M., Gambetti, S., Dondi, A. & Cervellati, C. Oxygen, reactive oxygen species and tissue

damage. _Curr. Pharm. Des._ 10, 1611–1626 (2004). Article  Google Scholar  * Shields, H. J., Traa, A. & Van Raamsdonk, J. M. Beneficial and detrimental effects of reactive oxygen species

on lifespan: a comprehensive review of comparative and experimental studies. _Front. Cell Dev. Biol._ 9, 628157 (2021). Article  Google Scholar  * Yarmolenko, P. S. et al. Thresholds for

thermal damage to normal tissues: an update. _Int. J. Hyperth._ 27, 320–343 (2011). Article  Google Scholar  * Sapareto, S. A. & Dewey, W. C. Thermal dose determination in cancer

therapy. _Int. J. Radiat. Oncol. Biol. Phys._ 10, 787–800 (1984). Article  Google Scholar  * Dewhirst, M. W., Viglianti, B., Lora-Michiels, M., Hanson, M. & Hoopes, P. Basic principles

of thermal dosimetry and thermal thresholds for tissue damage from hyperthermia. _Int. J. Hyperth._ 19, 267–294 (2003). Article  Google Scholar  * Sharma, H. Hyperthermia influences

excitatory and inhibitory amino acid neurotransmitters in the central nervous system. An experimental study in the rat using behavioural, biochemical, pharmacological, and morphological

approaches. _J. Neural Transm._ 113, 497–519 (2006). Article  Google Scholar  * Liebregts, M. T., McLachlan, R. S. & Leung, L. S. Hyperthermia induces age‐dependent changes in rat

hippocampal excitability. _Ann. Neurol._ 52, 318–326 (2002). Article  Google Scholar  * Johannsmeier, S. et al. Gold nanoparticle-mediated laser stimulation induces a complex stress response

in neuronal cells. _Sci. Rep._ 8, 6533 (2018). Article  Google Scholar  * Battaglini, M. et al. Polydopamine nanoparticles as an organic and biodegradable multitasking tool for

neuroprotection and remote neuronal stimulation. _ACS Appl. Mater. Interfaces_ 12, 35782–35798 (2020). Article  Google Scholar  * Carvalho-de-Souza, J. L. et al. Cholesterol

functionalization of gold nanoparticles enhances photoactivation of neural activity. _ACS Chem. Neurosci._ 10, 1478–1487 (2018). Article  Google Scholar  * DiFrancesco, M. L. et al. A hybrid

P3HT-graphene interface for efficient photostimulation of neurons. _Carbon_ 162, 308–317 (2020). Article  Google Scholar  * Yoo, S., Hong, S., Choi, Y., Park, J. H. & Nam, Y.

Photothermal inhibition of neural activity with near-infrared-sensitive nanotransducers. _ACS Nano_ 8, 8040–8049 (2014). THIS ARTICLE REPORTS THAT PHOTOTHERMAL INHIBITION INDUCED USING

NANOPARTICLES (GOLD NANORODS) CAN BE TUNED BY MODULATING THE ILLUMINATION CONDITIONS. Article  Google Scholar  * Lee, J. W., Jung, H., Cho, H. H., Lee, J. H. & Nam, Y. Gold

nanostar-mediated neural activity control using plasmonic photothermal effects. _Biomaterials_ 153, 59–69 (2018). Article  Google Scholar  * Kang, H., Lee, G.-H., Jung, H., Lee, J. W. &

Nam, Y. Inkjet-printed biofunctional thermo-plasmonic interfaces for patterned neuromodulation. _ACS Nano_ 12, 1128–1138 (2018). Article  Google Scholar  * Feyen, P. et al. Light-evoked

hyperpolarization and silencing of neurons by conjugated polymers. _Sci. Rep._ 6, 22718 (2016). Article  Google Scholar  * Lavoie-Cardinal, F., Salesse, C., Bergeron, É., Meunier, M. &

De Koninck, P. Gold nanoparticle-assisted all optical localized stimulation and monitoring of Ca2+ signaling in neurons. _Sci. Rep._ 6, 20619 (2016). Article  Google Scholar  * Eom, K. et

al. Photothermal activation of astrocyte cells using localized surface plasmon resonance of gold nanorods. _J. Biophotonics_ 10, 486–493 (2017). Article  Google Scholar  * Eom, K. et al.

Synergistic combination of near-infrared irradiation and targeted gold nanoheaters for enhanced photothermal neural stimulation. _Biomed. Opt. Express_ 7, 1614–1625 (2016). Article  Google

Scholar  * Nakatsuji, H. et al. Thermosensitive ion channel activation in single neuronal cells by using surface-engineered plasmonic nanoparticles. _Angew. Chem. Int. Ed._ 54, 11725–11729

(2015). Article  Google Scholar  * Paviolo, C., Haycock, J. W., Cadusch, P. J., McArthur, S. L. & Stoddart, P. R. Laser exposure of gold nanorods can induce intracellular calcium

transients. _J. Biophotonics_ 7, 761–765 (2014). Article  Google Scholar  * Grienberger, C. & Konnerth, A. Imaging calcium in neurons. _Neuron_ 73, 862–885 (2012). Article  Google

Scholar  * Jiang, Y. et al. Heterogeneous silicon mesostructures for lipid-supported bioelectric interfaces. _Nat. Mater._ 15, 1023–1030 (2016). Article  MathSciNet  Google Scholar  *

Miyako, E. et al. Photofunctional nanomodulators for bioexcitation. _Angew. Chem._ 126, 13337–13341 (2014). Article  Google Scholar  * Sakmann, B. & Neher, E. Patch clamp techniques for

studying ionic channels in excitable membranes. _Annu. Rev. Physiol._ 46, 455–472 (1984). Article  Google Scholar  * Tang, M. et al. Injectable black phosphorus nanosheets for wireless

nongenetic neural stimulation. _Small_ https://doi.org/10.1002/smll.202105388 (2021). Article  Google Scholar  * Jiang, S., Wu, X., Rommelfanger, N. J., Ou, Z. & Hong, G. Shedding light

on neurons: optical approaches for neuromodulation. _Natl Sci. Rev._ 9, nwac007 (2022). Article  Google Scholar  * Hong, G., Antaris, A. L. & Dai, H. Near-infrared fluorophores for

biomedical imaging. _Nat. Biomed. Eng._ 1, 0010 (2017). Article  Google Scholar  * Bashkatov, A. N., Genina, E., Kochubey, V. & Tuchin, V. Optical properties of human skin, subcutaneous

and mucous tissues in the wavelength range from 400 to 2000 nm. _J. Phys. D Appl. Phys._ 38, 2543 (2005). Article  Google Scholar  * Mie, G. Beiträge zur Optik trüber Medien, speziell

kolloidaler Metallösungen. _Ann. Phys._ 330, 377–445 (1908). Article  MATH  Google Scholar  * Rayleigh, J. W. S. B. _On the Scattering of Light by Small Particles_ (Cambridge University

Press, 1871). * Jung, H. & Nam, Y. Optical recording of neural responses to gold-nanorod mediated photothermal neural inhibition. _J. Neurosci. Methods_ 373, 109564 (2022). Article 

Google Scholar  * An, Y. & Nam, Y. Closed-loop control of neural spike rate of cultured neurons using a thermoplasmonics-based photothermal neural stimulation. _J. Neural Eng._ 18,

066002 (2021). Article  Google Scholar  * Lee, S. E., Liu, G. L., Kim, F. & Lee, L. P. Remote optical switch for localized and selective control of gene interference. _Nano Lett._ 9,

562–570 (2009). Article  Google Scholar  * Wijaya, A., Schaffer, S. B., Pallares, I. G. & Hamad-Schifferli, K. Selective release of multiple DNA oligonucleotides from gold nanorods. _ACS

Nano_ 3, 80–86 (2009). Article  Google Scholar  * Carrow, J. K. et al. Photothermal modulation of human stem cells using light-responsive 2D nanomaterials. _Proc. Natl Acad. Sci. USA_ 117,

13329–13338 (2020). THIS ARTICLE DEMONSTRATES PHOTOTHERMAL MODULATION OF GENE EXPRESSION AND CELLULAR FUNCTIONS IN HUMAN STEM CELLS USING 2D TRANSITION METAL DICHALCOGENIDES SUCH AS MOS2.

Article  Google Scholar  * Fricker, M., Tolkovsky, A. M., Borutaite, V., Coleman, M. & Brown, G. C. Neuronal cell death. _Physiol. Rev._ 98, 813–880 (2018). Article  Google Scholar  *

Lodola, F. et al. Conjugated polymers optically regulate the fate of endothelial colony-forming cells. _Sci. Adv._ 5, eaav4620 (2019). Article  Google Scholar  * Milos, F. et al. High aspect

ratio and light-sensitive micropillars based on a semiconducting polymer optically regulate neuronal growth. _ACS Appl. Mater. Interfaces_ 13, 23438–23451 (2021). Article  Google Scholar  *

Aziz, I. A. et al. Light-triggered electron transfer between a conjugated polymer and cytochrome C for optical modulation of redox signaling. _iScience_ 23, 101091 (2020). Article  Google

Scholar  * Huh, D., Hamilton, G. A. & Ingber, D. E. From 3D cell culture to organs-on-chips. _Trends Cell Biol._ 21, 745–754 (2011). Article  Google Scholar  * Lee, A. et al. 3D

bioprinting of collagen to rebuild components of the human heart. _Science_ 365, 482–487 (2019). Article  Google Scholar  * Kalmykov, A. et al. Bioelectrical interfaces with cortical

spheroids in three-dimensions. _J. Neural Eng._ 18, 055005 (2021). Article  Google Scholar  * Andersson, H. A., Kim, Y.-S., O’Neill, B. E., Shi, Z.-Z. & Serda, R. E. HSP70

promoter-driven activation of gene expression for immunotherapy using gold nanorods and near infrared light. _Vaccines_ 2, 216–227 (2014). Article  Google Scholar  * Chen, X., Chen, Y., Xin,

H., Wan, T. & Ping, Y. Near-infrared optogenetic engineering of photothermal nanoCRISPR for programmable genome editing. _Proc. Natl Acad. Sci. USA_ 117, 2395–2405 (2020). Article 

Google Scholar  * Fisher, R. S. & Velasco, A. L. Electrical brain stimulation for epilepsy. _Nat. Rev. Neurol._ 10, 261–270 (2014). Article  Google Scholar  * Ðerek, V., Rand, D.,

Migliaccio, L., Hanein, Y. & Głowacki, E. D. Untangling photofaradaic and photocapacitive effects in organic optoelectronic stimulation devices. _Front. Bioeng. Biotechnol._ 8, 284

(2020). Article  Google Scholar  * Medagoda, D. I. & Ghezzi, D. Organic semiconductors for light-mediated neuromodulation. _Commun. Mater._ 2, 111 (2021). Article  Google Scholar  *

Nair, V. et al. Laser writing of nitrogen-doped silicon carbide for biological modulation. _Sci. Adv._ 6, eaaz2743 (2020). Article  Google Scholar  * Alberts, B. _Molecular Biology of the

Cell_ (Garland Science, 2008). * Nicholls, J. G., Martin, A. R., Wallace, B. G. & Fuchs, P. A. _From Neuron to Brain_. Vol. 271 (Sinauer Associates Sunderland, 2001). * Paulsen, C. E.,

Armache, J.-P., Gao, Y., Cheng, Y. & Julius, D. Structure of the TRPA1 ion channel suggests regulatory mechanisms. _Nature_ 520, 511–517 (2015). Article  Google Scholar  * Crunelli, V.

& Leresche, N. A role for GABAB receptors in excitation and inhibition of thalamocortical cells. _Trends Neurosci._ 14, 16–21 (1991). Article  Google Scholar  * Mitragotri, S., Burke, P.

A. & Langer, R. Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. _Nat. Rev. Drug Discov._ 13, 655–672 (2014). Article  Google Scholar

  * Singh, R. & Lillard, J. W. Jr. Nanoparticle-based targeted drug delivery. _Exp. Mol. Pathol._ 86, 215–223 (2009). Article  Google Scholar  * Kim, C. Y. et al. Soft subdermal implant

capable of wireless battery charging and programmable controls for applications in optogenetics. _Nat. Commun._ 12, 535 (2021). Article  Google Scholar  * Ausra, J. et al. Wireless,

battery-free, subdermally implantable platforms for transcranial and long-range optogenetics in freely moving animals. _Proc. Natl Acad. Sci. USA_ 118, e2025775118 (2021). Article  Google

Scholar  * Reddy, J. W., Lassiter, M. & Chamanzar, M. Parylene photonics: a flexible, broadband optical waveguide platform with integrated micromirrors for biointerfaces. _Microsyst.

Nanoeng._ 6, 85 (2020). Article  Google Scholar  * Scopelliti, M. G. & Chamanzar, M. Ultrasonically sculpted virtual relay lens for in situ microimaging. _Light Sci. Appl._ 8, 65 (2019).

Article  Google Scholar  * Kim, D. et al. Ultraflexible organic light-emitting diodes for optogenetic nerve stimulation. _Proc. Natl Acad. Sci. USA_ 117, 21138–21146 (2020). Article  Google

Scholar  * Nel, A. E. et al. Understanding biophysicochemical interactions at the nano–bio interface. _Nat. Mater._ 8, 543–557 (2009). Article  Google Scholar  * Petros, R. A. &

DeSimone, J. M. Strategies in the design of nanoparticles for therapeutic applications. _Nat. Rev. Drug Discov._ 9, 615–627 (2010). Article  Google Scholar  * Benfenati, F. & Lanzani, G.

Clinical translation of nanoparticles for neural stimulation. _Nat. Rev. Mater._ 6, 1–4 (2021). Article  Google Scholar  * Charbgoo, F. et al. Gold nanoparticle should understand protein

corona for being a clinical nanomaterial. _J. Control. Rel._ 272, 39–53 (2018). Article  Google Scholar  Download references 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). AUTHOR INFORMATION Author notes * These authors contributed

equally: Yingqiao Wang, Raghav Garg. AUTHORS AND AFFILIATIONS * Department of Materials Science and Engineering, Carnegie Mellon University, Pittsburgh, PA, USA Yingqiao Wang, Raghav Garg 

& Tzahi Cohen-Karni * Preclinical education biochemistry, Lake Erie College of Osteopathic Medicine at Seton Hill, Greensburg, PA, USA Devora Cohen-Karni * Department of Biomedical

Engineering, Carnegie Mellon University, Pittsburgh, PA, USA Tzahi Cohen-Karni Authors * Yingqiao Wang View author publications You can also search for this author inPubMed Google Scholar *

Raghav Garg View author publications You can also search for this author inPubMed Google Scholar * Devora Cohen-Karni View author publications You can also search for this author inPubMed 

Google Scholar * Tzahi Cohen-Karni View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS Y.W. and R.G. contributed equally to this work.

CORRESPONDING AUTHOR Correspondence to Tzahi Cohen-Karni. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare that they have no known competing financial interests or personal

relationships that could have appeared to influence the work reported in this paper. PEER REVIEW PEER REVIEW INFORMATION _Nature Reviews Bioengineering_ thanks Guosong Hong, Diego Ghezzi,

and the other, anonymous, reviewer for their contribution to the peer review of this work. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to

jurisdictional claims in published maps and institutional affiliations. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION RIGHTS AND PERMISSIONS Springer Nature or its licensor (e.g. a

society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript

version of this article is solely governed by the terms of such publishing agreement and applicable law. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation *

Accepted: 02 January 2023 * Published: 31 January 2023 * Issue Date: March 2023 * DOI: https://doi.org/10.1038/s44222-023-00022-y SHARE THIS ARTICLE Anyone you share the following link with

will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt

content-sharing initiative