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Dual Behavior Regulation: Tether-Free Deep-Brain Stimulation by Photothermal and Upconversion Hybrid Nanoparticles
Advanced Materials ( IF 27.4 ) Pub Date : 2023-03-02 , DOI: 10.1002/adma.202210018
Feiyi Sun 1 , Hanchen Shen 1 , Qinghu Yang 2 , Zhaoyue Yuan 2 , Yuyang Chen 1 , Weihua Guo 3 , Yu Wang 2 , Liang Yang 2 , Zhantao Bai 2 , Qingqing Liu 4 , Ming Jiang 2 , Jacky W Y Lam 1 , Jianwei Sun 1 , Ruquan Ye 3 , Ryan T K Kwok 1 , Ben Zhong Tang 1, 5, 6
Affiliation  

Optogenetics has been plagued by invasive brain implants and thermal effects during photo-modulation. Here, two upconversion hybrid nanoparticles modified with photothermal agents, named PT-UCNP-B/G, which can modulate neuronal activities via photostimulation and thermo-stimulation under near-infrared laser irradiation at 980 nm and 808 nm, respectively, are demonstrated. PT-UCNP-B/G emits visible light (410–500 nm or 500–570 nm) through the upconversion process at 980 nm, while they exhibit efficient photothermal effect at 808 nm with no visible emission and tissue damage. Intriguingly, PT-UCNP-B significantly activates extracellular sodium currents in neuro2a cells expressing light-gated channelrhodopsin-2 (ChR2) ion channels under 980-nm irradiation, and inhibits potassium currents in human embryonic kidney 293 cells expressing the voltage-gated potassium channels (KCNQ1) under 808-nm irradiation in vitro. Furthermore, deep-brain bidirectional modulation of feeding behavior is achieved under tether-free 980 or 808-nm illumination (0.8 W cm−2) in mice stereotactically injected with PT-UCNP-B in the ChR2-expressing lateral hypothalamus region. Thus, PT-UCNP-B/G creates new possibility of utilizing both light and heat to modulate neural activities and provides a viable strategy to overcome the limits of optogenetics.

中文翻译:

双重行为调节:光热和上转换混合纳米粒子的无系绳深脑刺激

光遗传学一直受到侵入性脑植入和光调制过程中的热效应的困扰。在这里,展示了两种用光热剂修饰的上转换混合纳米粒子,名为 PT-UCNP-B/G,它们可以分别在 980 nm 和 808 nm 的近红外激光照射下通过光刺激和热刺激来调节神经元活动。PT-UCNP-B/G 通过 980 nm 的上转换过程发射可见光(410-500 nm 或 500-570 nm),而它们在 808 nm 表现出高效的光热效应,没有可见光发射和组织损伤。有趣的是,PT-UCNP-B 在 980 nm 照射下显着激活表达光门控视紫红质 2 (ChR2) 离子通道的 neuro2a 细胞中的细胞外钠电流,并在体外 808 nm 照射下抑制表达电压门控钾通道 (KCNQ1) 的人胚肾 293 细胞中的钾电流。此外,在无束缚的 980 或 808 nm 照明(0.8 W cm-2 ) 在表达 ChR2 的外侧下丘脑区域立体定向注射 PT-UCNP-B 的小鼠中。因此,PT-UCNP-B/G 创造了利用光和热来调节神经活动的新可能性,并提供了克服光遗传学局限性的可行策略。
更新日期:2023-03-02
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