Remote neurostimulation through an endogenous ion channel using a near-infrared light–activatable nanoagonist
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.
Authors
- Heng Liu (ORCID: https://orcid.org/0009-0009-5742-1539)
- Jian Yang (ORCID: https://orcid.org/0000-0003-0290-7688)
- Weifeng Tian (ORCID: https://orcid.org/0009-0009-8489-098X)
- Deyuan Su (ORCID: https://orcid.org/0000-0003-3287-9518)
- Yi Lu (ORCID: https://orcid.org/0000-0001-9182-853X)
- Yusheng Guo (ORCID: https://orcid.org/0000-0002-5826-299X)
- Min-Dong Xu (ORCID: https://orcid.org/0000-0001-5643-3364)
- Zhiyao Hou
- Chengjie Deng
- Shu Wang (ORCID: https://orcid.org/0000-0001-6383-3411)
- Ying Ye
- Wenjie Zhang (ORCID: https://orcid.org/0000-0001-6970-3909)
- Jingjing Liu (ORCID: https://orcid.org/0000-0001-8333-5233)
- Hao Wang (ORCID: https://orcid.org/0000-0003-1862-8229)
- Jianru Xiao (ORCID: https://orcid.org/0000-0003-1547-851X)
- Feiyu Chen (ORCID: https://orcid.org/0000-0002-6603-7987)
- Qi Jia (ORCID: https://orcid.org/0000-0002-8124-8432)
- Dongmei He (ORCID: https://orcid.org/0009-0002-4099-441X)
- Jiamin Luo (ORCID: https://orcid.org/0000-0003-2829-1914)
- Jiewen Lin
- Boxiang Cui
- Huiling Guo
- Jie Yang (ORCID: https://orcid.org/0000-0003-0423-4157)
Institutions
- Guangzhou University of Chinese Medicine (CN)
- Kunming Institute of Zoology (CN)
- Chinese Academy of Sciences (CN)
- Kunming Medical University (CN)
- Guangzhou University (CN)
- Second Affiliated Hospital of Guangzhou Medical University (CN)
- Shanghai Changzheng Hospital (CN)
- Guangdong Provincial Hospital of Traditional Chinese Medicine (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
- Columbia University (US)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Science Advances
- Published
- 2024-08-09
- DOI
- https://doi.org/10.1126/sciadv.adn0367
- Citations
- 9
- Primary Topic
- Photoreceptor and optogenetics research
- Type
- article
- Field-Weighted Citation Impact
- 2.41