Synthesis and Characterisation of Dual Functional Nanoparticles for Probing the Role of Reactive Oxygen Species in Cellular Function

该提案涉及双功能纳米颗粒的合成和表征，用于研究细胞对活性氧物种(ROS)的响应。ROS与衰老、心脏病有关，最近还与阿尔茨海默病的发病有关。这种纳米粒子将包含一种对钙离子变化做出反应的染料。钙离子是细胞用来将信息从一个部位发送到另一个部位的一种重要物种。我们的双功能纳米粒子将能够感知细胞内直接环境中钙离子的变化，但它们与其他类似物种的不同之处在于，当受到光刺激时，它们能够产生ROS爆发。在纳米颗粒形成后，产生ROS的成分将被附着在纳米颗粒上，并由称为卟啉的分子组成。目前，通过卟啉产生ROS的能力被用于癌症和老年性黄斑变性等疾病的光动力学治疗。通过改变卟啉的化学结构，然后将它们附着在纳米颗粒上，我们还计划使它们在细胞内的重要结构处积累，如线粒体。目前，还没有类似的工具可用于研究细胞中的ROS，预计我们系统的成功开发将产生与细胞如何响应ROS有关的重要新数据。

The proposal concerns the synthesis and characterisation of dual functional nanoparticles for studying the response of cells to Reactive Oxygen Species (ROS). ROS have been implicated in ageing, heart disease, and recently, in the onset of Alzheimer's disease. The nanoparticles will contain a dye which responds to changes in calcium ions. Calcium ions are an important species which the cell uses to send messages from one site to another. Our dual functional nanoparticles will have the ability to sense changes in calcium ions in their immediate environment within the cell, but what differentiates them from other similar species is the ability to generate bursts of ROS when excited with light. The ROS generating component will be attached to the nanoparticles after they are formed and are composed of molecules called porphyrins. The ability to generate ROS by porphyrins is currently exploited in the Photodynamic Therapy of diseases such as cancer and age related macular degeneration. By changing the chemical structure of the porphyrins and then attaching them to the nanoparaticle we also plan to cause them to accumulate at important structures within the cells, such as the mitochondria. Currently, no similar tools are available for studying ROS in cells and it is anticipated that the successful development of our system will generate important new data relating to how cells respond to ROS.