2. Academic Validation
  3. Remote neurostimulation through an endogenous ion channel using a near-infrared light-activatable nanoagonist

Remote neurostimulation through an endogenous ion channel using a near-infrared light-activatable nanoagonist

  • Sci Adv. 2024 Aug 9;10(32):eadn0367. doi: 10.1126/sciadv.adn0367.
Weifeng Tian 1 2 3 4,  Qi Jia 5,  Jiewen Lin 1,  Jiamin Luo 1,  Dongmei He 1,  Jie Yang 1,  Tao Guo 1,  Huiling Guo 1,  Yusheng Guo 6,  Wenjie Zhang 1,  Feiyu Chen 1,  Ying Ye 1,  Jingjing Liu 1,  Mindong Xu 1,  Chengjie Deng 7,  Boxiang Cui 1,  Deyuan Su 4,  Hao Wang 8,  Yi Lu 9,  Jianru Xiao 5,  Heng Liu 6,  Jian Yang 10,  Zhiyao Hou 1,  Shu Wang 1 2
Affiliations

Affiliations

  • 1 The Affiliated TCM Hospital of Guangzhou Medical University, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
  • 2 Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
  • 3 Institute of Organoid Technology, Kunming Medical University, Kunming, China.
  • 4 Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
  • 5 Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Second Affiliated Hospital of Naval Medical University, Shanghai, China.
  • 6 GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, The Affiliated TCM Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, GMU-GIBH Joint School of Life Sciences, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Guangzhou Medical University, Guangzhou, China.
  • 7 Cell Biology and Molecular Biology Laboratory of Experimental Teaching Center, Faculty of Basic Medical Science, Kunming Medical University, Kunming, China.
  • 8 Department of Neurobiology and Department of Neurosurgery of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 9 Department of Anesthesiology, The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University, Guangzhou, China.
  • 10 Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
PMID: 39121219 DOI: 10.1126/sciadv.adn0367
Abstract

The development of noninvasive approaches to precisely control neural activity in mammals is highly desirable. Here, we used the ion channel transient receptor potential ankyrin-repeat 1 (TRPA1) as a proof of principle, demonstrating remote near-infrared (NIR) activation of endogenous neuronal channels in mice through an engineered nanoagonist. This achievement enables specific neurostimulation in nongenetically modified mice. Initially, target-based screening identified flavins as photopharmacological agonists, allowing for the photoactivation of TRPA1 in sensory neurons upon ultraviolet A/blue light illumination. Subsequently, upconversion nanoparticles (UCNPs) were customized with an emission spectrum aligned to flavin absorption and conjugated with flavin adenine dinucleotide, creating a nanoagonist capable of NIR activation of TRPA1. Following the intrathecal injection of the nanoagonist, noninvasive NIR stimulation allows precise bidirectional control of nociception in mice through remote activation of spinal TRPA1. This study demonstrates a noninvasive NIR neurostimulation method with the potential for adaptation to various endogenous ion channels and neural processes by combining photochemical toolboxes with customized UCNPs.

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