Modulating Neurons via Optothermal, Magnetic, and Electrical Mechanisms Using Metal Nanoparticles

Abstract:

The nervous system plays a vital role in maintaining overall health. Recent nanotechnology advances enable precise control of neuronal activity using metal nanoparticles, which convert external stimuli into electrical, mechanical, or thermal signals to modulate excitability. This review explores three primary neuromodulation strategies (e.g., electrical, magnetic, and optothermal stimulation) where magnetic methods create magnetothermal and magnetomechanical effects, optothermal techniques use surface plasmon resonance to activate heat-sensitive ion channels, and electrical approaches alter membrane potential via the high conductivity of nanoparticles. These methods hold significant potential for treating neurological disorders such as chronic pain, epilepsy, and Parkinson’s disease, though challenges like biocompatibility, metal ion toxicity, and efficient nanoparticle clearance must be addressed. To overcome these barriers, ongoing research focuses on coating nanoparticles with protective layers, modifying their surfaces to improve safety, and designing them in ways that help the body clear them more easily. Incorporating targeted delivery systems, biodegradable materials, and stimuli-responsive coatings into nanoparticle design could further improve safety, enhance personalization, and enable precise, reversible control of brain circuits, opening new avenues for treating neurological conditions.

• Periodical: Journal of Biomimetics, Biomaterials and Biomedical Engineering (Volume 69)
• Pages: 81-91
• DOI: https://doi.org/10.4028/p-PMJe5k
• Online since: October 2025
• Authors: Muhammed Zahid Sahin*, Emre Uzun, Ibrahim Tekeoğlu
• Keywords: Electrical Stimulation, Magnetic Stimulation, Metal Nanoparticles, Neuromodulation, Optothermal Stimulation

References

[1] Gellini C, Feis A. Optothermal properties of plasmonic inorganic nanoparticles for photoacoustic applications. Photoacoustics 2021; 23: 100281.

DOI: 10.1016/j.pacs.2021.100281

[2] Huang H, Delikanli S, Zeng H, Ferkey DM, Pralle A. Remote control of ion channels and neurons through magnetic-field heating of nanoparticles. Nat Nanotechnol 2010;5:602–6.

DOI: 10.1038/nnano.2010.125

[3] Zhang Y, Chen S, Xiao Z, Liu X, Wu C, Wu K, et al. Magnetoelectric Nanoparticles Incorporated Biomimetic Matrix for Wireless Electrical Stimulation and Nerve Regeneration. Adv Healthc Mater 2021;10.

DOI: 10.1002/adhm.202100695

[4] Effects of Fe2+ Nanoparticles on Pain Responses and Neural Oscillation Following Chronic Neuropathic Pain in Rats. Arch Razi Inst 2023: 1852–60.

DOI: 10.32592/ARI.2023.78.6.1852

[5] Chen A, Kang Y, Liu J, Wu J, Feng X, Wang M, et al. Improvement of synaptic plasticity by nanoparticles and the related mechanisms: Applications and prospects. Journal of Controlled Release 2022;347:143–63.

DOI: 10.1016/j.jconrel.2022.04.049

[6] Kim DM, Nimigean CM. Voltage-Gated Potassium Channels: A Structural Examination of Selectivity and Gating. Cold Spring Harb Perspect Biol 2016; 8: a029231.

DOI: 10.1101/cshperspect.a029231

[7] Enyedi P, Czirják G. Molecular Background of Leak K + Currents: Two-Pore Domain Potassium Channels. Physiol Rev 2010;90:559–605. https://doi.org/10.1152/physrev. 00029.2009.

DOI: 10.1152/physrev.00029.2009

[8] Pirahanchi Y, Jessu R, Aeddula NR. Physiology, Sodium Potassium Pump. 2025.

[9] Platkiewicz J, Brette R. Impact of fast sodium channel inactivation on spike threshold dynamics and synaptic integration. PLoS Comput Biol 2011; 7: e1001129.

DOI: 10.1371/journal.pcbi.1001129

[10] Grider MH, Jessu R, Kabir R. Physiology, Action Potential. 2025.

[11] Peixoto HM, Cruz RMS, Moulin TC, Leão RN. Modeling the Effect of Temperature on Membrane Response of Light Stimulation in Optogenetically-Targeted Neurons. Front Comput Neurosci 2020; 14.

DOI: 10.3389/fncom.2020.00005

[12] Neumann W-J, Steiner LA, Milosevic L. Neurophysiological mechanisms of deep brain stimulation across spatiotemporal resolutions. Brain 2023; 146: 4456–68.

DOI: 10.1093/brain/awad239

[13] Jung J, Bungert A, Bowtell R, Jackson SR. Modulating Brain Networks With Transcranial Magnetic Stimulation Over the Primary Motor Cortex: A Concurrent TMS/fMRI Study. Front Hum Neurosci 2020; 14.

DOI: 10.3389/fnhum.2020.00031

[14] Xu S, Momin M, Ahmed S, Hossain A, Veeramuthu L, Pandiyan A, et al. Illuminating the Brain: Advances and Perspectives in Optoelectronics for Neural Activity Monitoring and Modulation. Advanced Materials 2023;35.

DOI: 10.1002/adma.202303267

[15] Zhi W, Li Y, Wang L, Hu X. Advancing Neuroscience and Therapy: Insights into Genetic and Non-Genetic Neuromodulation Approaches. Cells 2025; 14.

DOI: 10.3390/cells14020122

[16] Stoddart PR, Begeng JM, Tong W, Ibbotson MR, Kameneva T. Nanoparticle-based optical interfaces for retinal neuromodulation: a review. Front Cell Neurosci 2024;18.

DOI: 10.3389/fncel.2024.1360870

[17] Hammami I, Alabdallah NM, jomaa A Al, kamoun M. Gold nanoparticles: Synthesis properties and applications. J King Saud Univ Sci 2021;33:101560.

DOI: 10.1016/j.jksus.2021.101560

[18] Hoshyar N, Gray S, Han H, Bao G. The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction. Nanomedicine (Lond) 2016; 11: 673–92.

DOI: 10.2217/nnm.16.5

[19] Dong YC, Hajfathalian M, Maidment PSN, Hsu JC, Naha PC, Si-Mohamed S, et al. Effect of Gold Nanoparticle Size on Their Properties as Contrast Agents for Computed Tomography. Sci Rep 2019; 9: 14912.

DOI: 10.1038/s41598-019-50332-8

[20] Öztürk K, Kaplan M, Çalış S. Effects of nanoparticle size, shape, and zeta potential on drug delivery. Int J Pharm 2024;666:124799.

DOI: 10.1016/j.ijpharm.2024.124799

[21] Zhang XF, Liu ZG, Shen W, Gurunathan S. Silver nanoparticles: Synthesis, characterization, properties, applications, and therapeutic approaches. Int J Mol Sci 2016;17.

DOI: 10.3390/ijms17091534

[22] Bhana S, Lin G, Wang L, Starring H, Mishra SR, Liu G, et al. Near-Infrared-Absorbing Gold Nanopopcorns with Iron Oxide Cluster Core for Magnetically Amplified Photothermal and Photodynamic Cancer Therapy. ACS Appl Mater Interfaces 2015;7:11637–47.

DOI: 10.1021/acsami.5b02741

[23] Sela H, Cohen H, Elia P, Zach R, Karpas Z, Zeiri Y. Spontaneous penetration of gold nanoparticles through the blood brain barrier (BBB). J Nanobiotechnology 2015;13:71.

DOI: 10.1186/s12951-015-0133-1

[24] Guo Q, Xu S, Yang P, Wang P, Lu S, Sheng D, et al. A dual-ligand fusion peptide improves the brain-neuron targeting of nanocarriers in Alzheimer's disease mice. Journal of Controlled Release 2020; 320: 347–62.

DOI: 10.1016/j.jconrel.2020.01.039

[25] Yang P, Sheng D, Guo Q, Wang P, Xu S, Qian K, et al. Neuronal mitochondria-targeted micelles relieving oxidative stress for delayed progression of Alzheimer's disease. Biomaterials 2020; 238: 119844.

DOI: 10.1016/j.biomaterials.2020.119844

[26] Cheng X, Xie Q, Sun Y. Advances in nanomaterial-based targeted drug delivery systems. Front Bioeng Biotechnol 2023;11.

DOI: 10.3389/fbioe.2023.1177151

[27] Bruna T, Maldonado-Bravo F, Jara P, Caro N. Silver Nanoparticles and Their Antibacterial Applications. Int J Mol Sci 2021;22:7202.

DOI: 10.3390/ijms22137202

[28] Li H, Zou Y, Jiang J. Synthesis of Ag@CuO nanohybrids and their photo-enhanced bactericidal effect through concerted Ag ion release and reactive oxygen species generation. Dalton Transactions 2020;49:9274–81.

DOI: 10.1039/D0DT01816C

[29] Zhang T, Wang L, Chen Q, Chen C. Cytotoxic Potential of Silver Nanoparticles. Yonsei Med J 2014;55:283.

DOI: 10.3349/ymj.2014.55.2.283

[30] Beck F, Loessl M, Baeumner AJ. Signaling strategies of silver nanoparticles in optical and electrochemical biosensors: considering their potential for the point-of-care. Microchimica Acta 2023; 190: 91.

DOI: 10.1007/s00604-023-05666-6

[31] Abu Serea ES, Orue I, García JÁ, Lanceros-Méndez S, Reguera J. Enhancement and Tunability of Plasmonic-Magnetic Hyperthermia through Shape and Size Control of Au:Fe3O4 Janus Nanoparticles. ACS Appl Nano Mater 2023; 6: 18466–79.

DOI: 10.1021/acsanm.3c03818

[32] Cui X, Ruan Q, Zhuo X, Xia X, Hu J, Fu R, et al. Photothermal Nanomaterials: A Powerful Light-to-Heat Converter. Chem Rev 2023; 123: 6891–952.

DOI: 10.1021/acs.chemrev.3c00159

[33] Dheyab MA, Aziz AA, Moradi Khaniabadi P, Jameel MS, Oladzadabbasabadi N, Mohammed SA, et al. Monodisperse Gold Nanoparticles: A Review on Synthesis and Their Application in Modern Medicine. Int J Mol Sci 2022;23:7400.

DOI: 10.3390/ijms23137400

[34] Wang H, Siemens J. TRP ion channels in thermosensation, thermoregulation and metabolism. Temperature 2015;2:178–87.

DOI: 10.1080/23328940.2015.1040604

[35] Carvalho-de-Souza JL, Pinto BI, Pepperberg DR, Bezanilla F. Optocapacitive Generation of Action Potentials by Microsecond Laser Pulses of Nanojoule Energy. Biophys J 2018;114:283–8.

DOI: 10.1016/j.bpj.2017.11.018

[36] GIUSTINI AJ, PETRYK AA, CASSIM SM, TATE JA, BAKER I, HOOPES PJ. MAGNETIC NANOPARTICLE HYPERTHERMIA IN CANCER TREATMENT. Nano Life 2010;01:17–32.

DOI: 10.1142/S1793984410000067

[37] Chang D, Lim M, Goos JACM, Qiao R, Ng YY, Mansfeld FM, et al. Biologically Targeted Magnetic Hyperthermia: Potential and Limitations. Front Pharmacol 2018;9.

DOI: 10.3389/fphar.2018.00831

[38] Latypova AA, Yaremenko A V., Pechnikova NA, Minin AS, Zubarev I V. Magnetogenetics as a promising tool for controlling cellular signaling pathways. J Nanobiotechnology 2024;22:327.

DOI: 10.1186/s12951-024-02616-z

[39] Rubio Ayala M, Syrovets T, Hafner S, Zablotskii V, Dejneka A, Simmet T. Spatiotemporal magnetic fields enhance cytosolic Ca 2+ levels and induce actin polymerization via activation of voltage-gated sodium channels in skeletal muscle cells. Biomaterials 2018;163:174–84.

DOI: 10.1016/j.biomaterials.2018.02.031

[40] Boles MA, Engel M, Talapin D V. Self-Assembly of Colloidal Nanocrystals: From Intricate Structures to Functional Materials. Chem Rev 2016; 116: 11220–89.

DOI: 10.1021/acs.chemrev.6b00196

[41] Wang Y, Lin J, Zhu K, Nie Y, Wang M, Ma X, et al. Precision neuroregulation combining liquid metal and magnetic stimulation. J Neuroeng Rehabil 2025;22:76.

DOI: 10.1186/s12984-025-01575-2

[42] Young AT, Cornwell N, Daniele MA. Neuro‐Nano Interfaces: Utilizing Nano‐Coatings and Nanoparticles to Enable Next‐Generation Electrophysiological Recording, Neural Stimulation, and Biochemical Modulation. Adv Funct Mater 2018; 28.

DOI: 10.1002/adfm.201700239

[43] Nakamura H, Sezawa K, Hata M, Ohsaki S, Watano S. Direct translocation of nanoparticles across a model cell membrane by nanoparticle-induced local enhancement of membrane potential. Physical Chemistry Chemical Physics 2019; 21: 18830–8.

DOI: 10.1039/C9CP02935D

[44] Kricheldorff J, Göke K, Kiebs M, Kasten FH, Herrmann CS, Witt K, et al. Evidence of Neuroplastic Changes after Transcranial Magnetic, Electric, and Deep Brain Stimulation. Brain Sci 2022;12:929.

DOI: 10.3390/brainsci12070929

[45] Chacron MJ, Fortune ES. Subthreshold Membrane Conductances Enhance Directional Selectivity in Vertebrate Sensory Neurons. J Neurophysiol 2010;104:449–62.

DOI: 10.1152/jn.01113.2009

[46] Zhang X-F, Liu Z-G, Shen W, Gurunathan S. Silver Nanoparticles: Synthesis, Characterization, Properties, Applications, and Therapeutic Approaches. Int J Mol Sci 2016;17:1534.

DOI: 10.3390/ijms17091534

[47] Bliss TVP, Cooke SF. Long-term potentiation and long-term depression: a clinical perspective. Clinics 2011;66:3–17.

DOI: 10.1590/S1807-59322011001300002

[48] Cunningham B, Engstrom AM, Harper BJ, Harper SL, Mackiewicz MR. Silver Nanoparticles Stable to Oxidation and Silver Ion Release Show Size-Dependent Toxicity In Vivo. Nanomaterials 2021;11:1516.

DOI: 10.3390/nano11061516

[49] Sun C, Yin N, Wen R, Liu W, Jia Y, Hu L, et al. Silver nanoparticles induced neurotoxicity through oxidative stress in rat cerebral astrocytes is distinct from the effects of silver ions. Neurotoxicology 2016;52:210–21.

DOI: 10.1016/j.neuro.2015.09.007

[50] Guo F, Nie X, Hong J, Zhang Y, Sun J, Zhang Y. Influence of Joule heating during single-cell electroporation simulation under IRE and H-FIRE pulses. Mater Today Commun 2023;36:106853.

DOI: 10.1016/j.mtcomm.2023.106853

[51] Mickle AD, Shepherd AJ, Mohapatra DP. Sensory TRP Channels, 2015, p.73–118.

DOI: 10.1016/bs.pmbts.2015.01.002

[52] Guo B, Zhang M, Hao W, Wang Y, Zhang T, Liu C. Neuroinflammation mechanisms of neuromodulation therapies for anxiety and depression. Transl Psychiatry 2023;13:5.

DOI: 10.1038/s41398-022-02297-y