Responsive, biocompatible lanthanide-nanoparticle conjugates for enhanced imaging

锌的传感器非常有趣，因为这种金属离子对人体生长发育至关重要。特别是，可以监测细胞内水平的分子探针很有吸引力，因为它们可以提高我们对阿尔茨海默病等退行性疾病发展的理解，也可以提高我们对乳腺癌、糖尿病甚至哮喘等更常见疾病的理解。例如，锌转运蛋白在乳腺癌的发展中起着不可思议的重要作用，也许更重要的是这些癌症如何对治疗产生抗药性。我们有兴趣使用非侵入性成像技术，如荧光和磁共振成像（MRI），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的检测，这些荧光染料是基于有机化合物，如喹啉衍生物。然而，它们在光谱的绿色部分是荧光的。这对生物化学家和药剂师来说是一个问题，他们在研究中经常使用绿色荧光蛋白。通常很难区分绿色荧光蛋白和锌染料。因此，我们正在开发易于与绿色荧光蛋白和其他荧光生物分子区分的锌荧光物质。我们的化合物是基于金属配合物（特别是镧系金属离子），它们具有非常独特的发光特性，非常适合于生物学研究（它们具有很长的荧光半衰期，可以在光谱中水不强烈吸收的区域发射）。最后我们要把这些分子组装成纳米粒子。纳米粒子将作为荧光染料的稳定转运体，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，也适用于MRI。通过对分子进行一个微不足道的改变（即将镧系金属离子的类型改变为钆），这些试剂也将适用于MRI成像。该项目的关键在于了解如何在锌存在的情况下切换信号响应，设计水溶性无毒化合物，并了解相关的成像技术。在项目结束时，我们希望在卡迪夫大学同事的帮助下，对细胞中的锌进行成像，并帮助了解锌在乳腺癌中的作用。

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.