Near-IR Fluorescence Sensors for Zn2+ based on Single-Walled Carbon Nanotubes

描述(由申请人提供)：在各种细胞内和细胞外环境中发现了游离锌离子池，通常与活体中的信号事件有关。锌蓄积模式的紊乱与糖尿病、癌症和阿尔茨海默病等神经退行性疾病有关；然而，这种离子在这些病理过程和一系列生理功能中的具体作用仍然知之甚少。更好的成像技术的发展，允许研究广泛的生物样品中的游离锌离子，对于解决许多关于锌生物学的悬而未决的问题是至关重要的。本文概述的研究方案侧重于设计和开发新的荧光探针，用于检测生物样品中的游离锌离子，在电磁光谱的近红外区产生光学响应。该策略是基于单壁碳纳米管(SWCNT)的近红外荧光特性的调制，利用吸附在单壁碳纳米管管壁上的寡核苷酸偶联物的构象变化。专门设计用于螯合锌离子的合成核苷酸被掺入寡核苷酸序列中，以赋予SWCNT-寡核苷酸复合体与锌的特异结合能力。选择荧光团(SWCNT)和锌结合部分旨在解决移动锌成像中迄今尚未解决的一个重要挑战：将传感器的光学响应调整到更适合活体应用的光谱窗口，背景干扰更少，组织渗透率更高，对细胞组件的损害更小。

DESCRIPTION (provided by applicant): Pools of free zinc ion have been found in a variety of intra- and extracellular environments, often linked to signaling events in living organisms. Disrupted patterns of zinc accumulation have been associated with diabetes, cancer, and neurodegenerative diseases such as Alzheimer's disease; nevertheless, the specific role of this ion in such pathological process and in a range of physiological functions remains poorly understood. The development of better imaging techniques that allow for the study of free Zn2+ in a wide range of biological samples is crucial in solving many of the unanswered questions about zinc biology. The research proposal outlined herein focuses on the design and development of new fluorescent probes for the detection of free Zn2+ in biological samples, producing an optical response in the Near-Infrared region of the electromagnetic spectrum. The proposed strategy is based on the modulation of the Near-Infrared fluorescence properties of Single-Walled Carbon Nan tubes (SWCNT), taking advantage of conformational changes of oligonucleotide conjugates adsorbed to the tube's walls. Synthetic nucleotides, specifically designed to chelate Zn2+, are incorporated into oligonucleotide sequences in order to confer zinc-specific binding capabilities to the SWCNT-oligonucleotide complex. The choice of fluorophore (SWCNT) and zinc- binding moiety seeks to address an important and thus far unsolved challenge in mobile Zn2+ imaging: the tuning of the sensor's optical response to a spectral window more suitable for in vivo applications, with less background interference, higher tissue penetration, and less damage to cellular components.