Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications, Nanjing, 210023, China.
Shaanxi Institute of Flexible Electronics (SIFE), Northwestern Polytechnical University (NPU), Xi'an, 710072, China.
Small. 2018 Mar;14(11):e1703400. doi: 10.1002/smll.201703400. Epub 2018 Jan 10.
As one of the reduction species, glutathione (GSH) plays a tremendous role in regulating the homeostasis of redox state in living body. Accurate imaging of GSH in vivo is highly desired to provide a real-time visualization of physiological and pathological conditions while it is still a big challenge. Recently developed photoacoustic imaging (PAI) with high resolution and deep penetration characteristics is more promising for in vivo GSH detection. However, its application is dramatically limited by the difficult designation of photoacoustic probes with changeable near-infrared (NIR)-absorption under reductive activation. A cyanine derivative-based activatable probe is developed for in vivo ratiometric PAI of GSH for the first time. The probe is structurally designed to output ratiometric signals toward GSH in NIR-absorption region based on the cleavage of disulfide bond followed by a subsequent exchange between the secondary amine and sulfydryl group formed. Such a ratiometric manner provides high signal-to-noise imaging of blood vessels and their surrounding areas in tumor. Concomitantly, it also exhibits good specificity toward GSH over other thiols. Furthermore, the single composition architecture of the probe effectively overcomes the leakage issue compared with traditional multicomposition architecture-based nanoprobe, thus enhancing the imaging accuracy and fidelity in living body.
作为还原物质之一，谷胱甘肽（GSH）在调节生物体内氧化还原状态的动态平衡中发挥着巨大的作用。准确地对活体中的 GSH 进行成像，以提供生理和病理状态的实时可视化，这仍然是一个巨大的挑战。最近开发的具有高分辨率和深穿透特性的光声成像（PAI）技术，更有望用于活体 GSH 检测。然而，由于还原激活下近红外（NIR）吸收变化的光声探针的设计困难，其应用受到了极大的限制。本文首次开发了基于菁染料的可激活探针，用于活体 GSH 的比率型光声成像。该探针的结构设计是基于二硫键的断裂，随后形成的仲胺基和巯基之间的交换，在近红外吸收区域输出针对 GSH 的比率型信号。这种比率型方式提供了对肿瘤血管及其周围区域的高信噪比成像。同时，它对 GSH 也表现出了比其他巯基化合物更好的特异性。此外，与传统的基于多组分架构的纳米探针相比，该探针的单一组成架构有效地克服了漏液问题，从而提高了活体中的成像准确性和保真度。
