State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin, 541004, China.
Research Laboratory for Biomedical Optics and Molecular Imaging, CAS Key Laboratory of Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Anal Chem. 2020 May 5;92(9):6382-6390. doi: 10.1021/acs.analchem.9b05431. Epub 2020 Mar 18.
As a noninvasive deep-tissue imaging technique, photoacoustic (PA) imaging has great application potential in biomedicine and molecular diagnosis. The zinc ion (Zn), which is a necessary metal ion in the human body, plays a very important role in the regulation of gene transcription and metalloenzyme function. The imbalance of Zn homeostasis is also associated with a variety of neurological diseases. Therefore, it is critically important to accurately image the steady-state changes of Zn in vivo. However, no PA imaging method is currently available for Zn. To this end, we designed and synthesized the first PA probe of Zn, namely, CR-1 for in situ ratiometric imaging of Zn in deep tissue in vivo. The CR-1molecule, combined with Zn, weakened the conjugation system of the π-electron in the CR-1 molecule, which resulted in the blue shift of its absorption peak from 710 nm to 532 nm. The PA signal intensity decreased at 710 nm and increased at 532 nm, and the ratiometric PA signal at these two wavelengths (PA/PA) showed a good linear relationship with the concentration of Zn in the range of 0-50 μM, with a detection limit as low as 170 nM. Furthermore, this probe exhibits extremely fast responsiveness, is highly selective, and has excellent biocompatibility. We have used the developed PA probe for the ratiometric PA imaging of Zn in the thigh tissue of mice, and we still can accurately image Zn after covering chicken breast tissue on the surface of mice thigh. In light of these outstanding features, the developed PA probe has high potential for imaging Zn in deep tissues; thus, it will open up new avenues for the study of the complex biochemical processes involving Zn in vivo.
作为一种非侵入性的深层组织成像技术，光声（PA）成像在生物医学和分子诊断中有很大的应用潜力。锌离子（Zn）是人体必需的金属离子，在基因转录和金属酶功能的调节中起着非常重要的作用。Zn 内稳态的失衡也与多种神经疾病有关。因此，准确地对体内 Zn 的稳态变化进行成像至关重要。然而，目前还没有用于 Zn 的 PA 成像方法。为此，我们设计并合成了第一个 Zn 的 PA 探针，即 CR-1，用于在体内在深层组织中对 Zn 进行原位比率成像。CR-1 分子与 Zn 结合后，削弱了 CR-1 分子中π电子的共轭体系，导致其吸收峰从 710nm 蓝移至 532nm。PA 信号强度在 710nm 处降低，在 532nm 处增加，并且这两个波长（PA/PA）的比率 PA 信号与 Zn 的浓度在 0-50μM 范围内呈良好的线性关系，检测限低至 170nM。此外，该探针表现出极快的响应性、高度选择性和优异的生物相容性。我们已经使用开发的 PA 探针对小鼠大腿组织中的 Zn 进行了比率 PA 成像，并且在小鼠大腿表面覆盖鸡胸组织后，仍能准确地对 Zn 进行成像。鉴于这些突出的特点，开发的 PA 探针具有对深层组织中 Zn 进行成像的巨大潜力；因此，它将为研究体内涉及 Zn 的复杂生化过程开辟新的途径。
