Abstract：
In vivo transmembrane-voltage detection reflected the electrophysiological activities of the biological system, which is crucial for the diagnosis of neuronal disease. Traditional implanted electrodes can only monitor limited regions and induce relatively large tissue damage. Despite emerging monitoring methods based on optical imaging have access to signal recording in a larger area, the recording wavelength of less than 1000 nm seriously weakens the detection depth and resolution in vivo. Herein, a Förster resonance energy transfer (FRET)-based nano-indicator, NaYbF4:Er@NaYF4@Cy7.5@DPPC (Cy7.5-ErNP) with emission in the near-infrared IIb biological window (NIR-IIb, 1500-1700 nm) is developed for transmembrane-voltage detection. Cy7.5 dye is found to be voltage-sensitive and is employed as the energy donor for the energy transfer to the lanthanide nanoparticle, NaYbF4:Er@NaYF4 (ErNP), which works as the acceptor to achieve electrophysiological signal responsive NIR-IIb luminescence. Benefiting from the high penetration and low scattering of NIR-IIb luminescence, the Cy7.5-ErNP enables both the visualization of action potential in vitro and monitoring of Mesial Temporal lobe epilepsy (mTLE) disease in vivo. This work presents a concept for leveraging the lanthanide luminescent nanoprobes to visualize electrophysiological activity in vivo, which facilitates the development of an optical nano-indicator for the diagnosis of neurological disorders.
摘要：
体内跨膜电压检测反映了生物系统的电生理活动,这对神经元疾病的诊断至关重要。传统的植入电极只能监测有限的区域并引起相对较大的组织损伤。尽管新兴的基于光学成像的监测方法可以在更大的区域内进行信号记录，小于1000nm的记录波长严重削弱了体内的检测深度和分辨率。在这里，一种基于Förster共振能量转移(FRET)的纳米指示剂，NaYbF4：Er@NaYF4@Cy7.5@DPPC（Cy7.5-ErNP），在近红外IIb生物窗口中发射（NIR-IIb，1500-1700nm）用于跨膜电压检测。发现Cy7.5染料是电压敏感的，并用作能量转移到镧系元素纳米颗粒的能量供体，NaYbF4:Er@NaYF4(ErNP),其作为受体来实现电生理信号响应NIR-IIb发光。受益于NIR-IIb发光的高穿透性和低散射，Cy7.5-ErNP可以在体外可视化动作电位，并在体内监测内侧颞叶癫痫（mTLE）疾病。这项工作提出了利用镧系元素发光纳米探针可视化体内电生理活性的概念。这有助于开发用于诊断神经系统疾病的光学纳米指示剂。
