In vitro and in vivo fate of composite nanoparticles observed in situ with triple labelling techniques

无机纳米粒子被细胞/生物体吸收后的命运将被研究。将开发两种材料系统。单个纳米颗粒将包括一个无机核心，一个有机表面涂层，作为吸附蛋白质的电晕。将开发所有部分的三重标签，即核心，表面涂层和蛋白质电晕。复合纳米颗粒将包括多个单独的无机纳米颗粒嵌入/集成在聚合物基质中，周围是吸附蛋白质的电晕。将开发所有部分的三重标记，即无机纳米颗粒的核心和表面以及聚合物基质。将使用不同检测方式的标签，包括荧光，SERS， MRI， SPECT和PET。细胞和有机体（水螅、鸡胚胎）将暴露在纳米颗粒中。纳米颗粒的所有单个化合物的命运和生物分布将被追踪，允许观察纳米颗粒在细胞/生物体内可能的降解。通过这种方式，物理化学性质，特别是纳米颗粒的完整性将不是在颗粒内化之前，而是在颗粒内化之后确定的。这些结果将有助于更好地理解被动靶向与主动靶向的概念，例如，解决纳米颗粒周围有机表面涂层的降解是否会干扰主动靶向的问题。此外，将研究递送复合纳米颗粒的策略，这些纳米颗粒大到足以被动靶向，但在降解成其成分后又小到足以完全排出体外。除了为成像提供对比度的标签外，还将使用主动标签，它们根据局部环境改变信号。通过这种方式，将实现对纳米颗粒所有成分周围的局部环境的持续监测（例如探测ROS）。

The fate of inorganic nanoparticles after their uptake by cells/organisms will be investigated. Two material systems will be developed. Individual nanoparticles will comprise an inorganic core, an organic surface coating, as a corona of adsorbed proteins. Triple labelling of all parts, i.e. core, surface coating, and protein corona, will be developed. Composite nanoparticles will comprise multiple individual inorganic nanoparticles embedded/integrated in a polymer matrix, surrounded by a corona of adsorbed proteins. Triple labelling of all parts, i.e. core and surface of the inorganic nanoparticles, and the polymer matrix, will be developed. Labels for different detection modalities comprising fluorescence, SERS, MRI, SPECT, and PET will be used. Cells and organisms (hydra, chicken embryos) will be exposed to the nanoparticles. The fate and biodistribution of all individual compounds of the nanoparticles will be traced, allowing for observing possible degradation of the nanoparticles inside cells/organisms. In this way physicochemical properties, as in particular integrity of the nanoparticles will be determined not before, but after internalization of the particles. The results will help to better understand the concept of passive versus active targeting, e.g. address the question whether degradation of the organic surface coating around nanoparticles interferes with active targeting. In addition the strategy to deliver composite nanoparticles which are big enough for passive targeting, but which after degradation to their components are small enough for complete excretion, will be investigated. Besides labels providing contrast for imaging also active labels will be used, which change their signal in dependence of their local environment. In this way a constant monitoring of the local environment around all the components of the nanoparticles will be achieved (such as probing for ROS).