Responsive, biocompatible lanthanide-nanoparticle conjugates for enhanced imaging

锌的传感器是非常感兴趣的，因为这种金属离子是人类生长和发育所必需的。特别是，允许监测细胞内水平的分子探针是有吸引力的，因为它们可以改善我们对退行性疾病（如阿尔茨海默病）发展的理解，而且还可以改善更常见的疾病（如乳腺癌，糖尿病甚至哮喘）。例如，锌转运蛋白在乳腺癌的发展中非常重要，也许在这些癌症如何对治疗产生耐药性方面更为重要。后者是医院中最常用的成像技术之一。目前有一些荧光染料用于锌检测，这些基于有机化合物如喹啉衍生物。然而，这些在光谱的绿色部分是荧光的。这对于在研究中常规使用绿色荧光蛋白的生物化学家和药剂师来说是个问题。通常很难区分绿色荧光蛋白和锌染料。因此，我们正在开发锌的荧光物种，可以很容易地区分绿色荧光蛋白和其他荧光生物分子。我们的化合物基于金属络合物（特别是镧系金属离子），这些化合物具有非常独特的发光特性，非常适合生物学研究（它们具有长的荧光半衰期，并且可以在水不强烈吸收的光谱区域发射）。最后，我们将把这些分子组装成纳米颗粒。这种纳米颗粒将作为荧光染料的稳定转运体，并有望增强染料的特性，从而改善信号。这些系统经过专门设计，不仅适用于荧光成像，而且适用于MRI。通过对分子做一个微小的改变（即，将镧系金属离子的类型改变为钆）试剂也将适用于MRI成像。该项目的潜在关键是了解如何在锌的存在下切换信号响应，设计水溶性，非有毒化合物，并了解相关的成像技术。在项目结束时，我们希望能成像锌在细胞中的作用，并帮助了解锌的作用在卡迪夫的同事的帮助下，

Sensors for zinc are of great interest since this metal ion is essential for human growth and development. In particular, molecular probes that allow monitoring of intracellular levels are attractive because they can inprove our understanding of the development of degenerative conditions such as Alzheimer's disease, but also more common conditions such as breast cancer, diabetes and even asthma. For example zinc transporters are known to be incredibly important in the devlopment of breast cancer and perhaps even more inportantly how these cancers become resistant to therapies.We are interested in using non-invasive imaging techniques such as fluorescence and magnetic resonance imaging (MRI) the latter of which is one of the most common imaging techniques used in hospitals.Currently there are some fluorescent dyes used for zinc detection and these are based on organic compounds such as quinoline derivatives. However these are fluorescent in the green part of the spectrum. This is a problem for biochemists and pharmacists who routinely use green fluorescent protein in their studies. Usually it is very difficult to differentiate between the green fluorescent protein and the zinc dye. Therefore we are developing fluorescent species for zinc that can be easily differentiated from green fluorescent protein and otehr fluorescent bio-molecules. Our compounds are based upon metal complexes (in particular lanthanide metal ions) and these have very unique luminescence characteristics which are highly suited to biological studies (they have long fluorescence half-lifes and can be emissive in regions of the spectrum where water does not absorb strongly). Finally we are going to be assembling these molecules to nanoparticles. The nanoparticle will act as a stable transporter for the fluorescent dyes and will hopefully enhance the characteristics of the dye thus improving the signal.These systems have been specifically designed to be applicable to not only fluorescent imaging but also to MRI. By literally making one trivial change to the molecule (i.e. changing the type of lanthanide metal ion to gadolinium) the agents will be applicable to MRI imaging as well.The underlying key to the project is understanding how to switch signal response in the presence of zinc, design water soluble, non-toxic compounds and understand the associated imaging techniques.By the end of the project we hope to be imaging zinc in cells and helping to understand the role of zinc in breast cancer, with the help of colleagues at Cardiff.