Nanomaterial-genetics enables near-infrared-driven genetically targeted neuromodulation
6 affiliations
- 1Zhongshan School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen 518107, China.
- 2IDG/McGovern Institute for Brain Research, School of Basic Medical Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
- 3Neuropharmacology Platform of the Center of Pharmaceutical Technology, Tsinghua University, Beijing 100084, China.
- 4State Key Laboratory of Cryogenic Science and Technology and Beijing Key Laboratory of Cryobiomedicine, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
- 5School of Flexible Electronics (SoFE) and State Key Laboratory of Optoelectronic Materials and Technologies (OEMT), Sun Yat-sen University, Shenzhen 518107, China.
- 6School of Life Sciences, Yunnan University, Kunming 650091, China.
Abstract
Stimuli-responsive nanomaterials offer powerful capabilities for neuromodulation, yet there is a continuous need for more versatile methods to ensure cell-specific targeting, a prerequisite for their precise application in neuroscience. To address this gap, we introduce the nanomaterial-genetics (NMG) system, a strategy that integrates genetically encoded synthetic receptors with ligand-functionalized nanoparticles to achieve receptor-guided, cell-selective targeting. Neurons are engineered to express an NMG Receptor carrying an extracellular HaloTag, which selectively captures HaloTag ligand-functionalized gold nanoparticles (AuNP-Ligands). This genetically encoded receptor-ligand pairing enables efficient and localized nanomaterial-mediated photothermal activation under near-infrared (NIR) irradiation at ultralow nanoparticle doses, whereas receptor-negative neurons remain largely unresponsive. Receptor-guided targeting substantially reduces nanomaterial-associated cytotoxicity under the tested conditions while preserving robust neuromodulatory efficacy. We demonstrate genetically targeted activation of neurons in vitro and in vivo, including transcranial NIR modulation of mouse locomotor behavior. Collectively, the NMG system offers an extensible complement to current neuromodulation technologies, providing a versatile platform for multimodal and precision neuromodulation.
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BibTeX
@article{liu2026nanomaterialgenetics,
title = {{Nanomaterial-genetics enables near-infrared-driven genetically targeted neuromodulation}},
author = {Yi Liu and Xiaolei Wang and Weiwei Yin and Jiahui Chen and Yu Fan and Jiani Yang and Yu Wang and Lin Ge and Wei Rao and Laiyuan Wang and Cheng Li and Zengcai V. Guo and Nan Liu and Xuyang Sun and Yaxiong Yang},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aef7843},
url = {https://www.science.org/doi/abs/10.1126/sciadv.aef7843},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Nanomaterial-genetics enables near-infrared-driven genetically targeted neuromodulation
AU - Yi Liu
AU - Xiaolei Wang
AU - Weiwei Yin
AU - Jiahui Chen
AU - Yu Fan
AU - Jiani Yang
AU - Yu Wang
AU - Lin Ge
AU - Wei Rao
AU - Laiyuan Wang
AU - Cheng Li
AU - Zengcai V. Guo
AU - Nan Liu
AU - Xuyang Sun
AU - Yaxiong Yang
PY - 2026
DA - 2026/10/28
JO - Science Advances
DO - 10.1126/sciadv.aef7843
UR - https://www.science.org/doi/abs/10.1126/sciadv.aef7843
AB - Stimuli-responsive nanomaterials offer powerful capabilities for neuromodulation, yet there is a continuous need for more versatile methods to ensure cell-specific targeting, a prerequisite for their precise application in neuroscience. To address this gap, we introduce the nanomaterial-genetics (NMG) system, a strategy that integrates genetically encoded synthetic receptors with ligand-functionalized nanoparticles to achieve receptor-guided, cell-selective targeting. Neurons are engineered to express an NMG Receptor carrying an extracellular HaloTag, which selectively captures HaloTag ligand-functionalized gold nanoparticles (AuNP-Ligands). This genetically encoded receptor-ligand pairing enables efficient and localized nanomaterial-mediated photothermal activation under near-infrared (NIR) irradiation at ultralow nanoparticle doses, whereas receptor-negative neurons remain largely unresponsive. Receptor-guided targeting substantially reduces nanomaterial-associated cytotoxicity under the tested conditions while preserving robust neuromodulatory efficacy. We demonstrate genetically targeted activation of neurons in vitro and in vivo, including transcranial NIR modulation of mouse locomotor behavior. Collectively, the NMG system offers an extensible complement to current neuromodulation technologies, providing a versatile platform for multimodal and precision neuromodulation.
SN - 2375-2548
ER -