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

描述（由申请人提供）：已在多种细胞内和细胞外环境中发现游离锌离子的释放，其通常与活生物体中的信号传导事件有关。锌积累的破坏模式与糖尿病、癌症和神经退行性疾病如阿尔茨海默病有关;然而，这种离子在这种病理过程和一系列生理功能中的具体作用仍然知之甚少。开发更好的成像技术，允许研究各种生物样品中的游离Zn 2+，对于解决许多关于锌生物学的未解答问题至关重要。本文概述的研究建议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Zn 2+，在电磁波谱的近红外区域产生光学响应。所提出的策略是基于单壁碳纳米管（SWCNT）的近红外荧光特性的调制，利用吸附到管壁的寡核苷酸缀合物的构象变化。专门设计用于螯合Zn 2+的合成核苷酸被掺入寡核苷酸序列中，以赋予SWCNT-寡核苷酸复合物锌特异性结合能力。荧光团（SWCNT）和锌结合部分的选择寻求解决移动的Zn 2+成像中的重要且迄今未解决的挑战：将传感器的光学响应调谐到更适合于体内应用的光谱窗口，具有更少的背景干扰、更高的组织穿透性和对细胞组分的更少损伤。

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.