Near-Infrared-II Chemo-Optogenetics for Deep-Brain Stimulation

We introduced a near-infrared II (NIR-II)-mediated optogenetic neuromodulation inspired by HaloTag self-labelling system (HaloNeu). An engineered temperature-sensitive ion channel HaloTag-TRPV1 was developed and stably targeted activation through NIR-II photothermal conversion nanoparticles functionalized with HaloTag chloroalkane ligands in vivo by irreversible covalent bond formation. This allowed non-invasive, long-term stable and cell-type specific neuromodulation and behavioral manipulation by low and safe power of NIR-II illumination. Moreover, the HaloNeu approach enables precise activation of VTA-triggered neural circuits, offering effective and stable intervention on symptoms of Parkinson’s disease (PD).

本研究提出了一种受HaloTag自标记系统（HaloTag）启发的、基于近红外二区（NIR-II）的光遗传神经调控方法（HaloNeu）。研究开发了工程化温度敏感离子通道HaloTag-TRPV1，并通过表面修饰有HaloTag氯烷配体的NIR-II光热转换纳米颗粒，在体内借助不可逆共价键形成实现稳定的靶向激活。该方法可通过低功率且安全的NIR-II照射，实现非侵入性、长期稳定且细胞类型特异性的神经调控与行为操控。此外，HaloNeu方案能够精准激活腹侧被盖区（VTA）介导的神经环路，可为帕金森病（PD）的症状提供有效且稳定的干预手段。