Smart sensor particles for intracellular tracing of reactive oxygen species by transmission electron microscopy

Reactive oxygen species (ROS) are important markers for understanding the cellular condition in the context of diseases and inflammatory reactions to nanoparticle uptake. Their precise localization in the cellular context by high resolution microscopy, such as Transmission Electron Microscopy, is an essential tool to visualize ultrastructural alterations and the formation of ROS. However, till now, only limited staining strategies for the TEM investigation of ROS are applied to identify them into the cellular context which are moreover associate to inherent problems of the staining procedure, such as high toxicity and unspecific precipitation in certain cultivation media. Here we report the development of a novel sensor particle system, which allows intracellular detection of ROS. These sensor particles link cerium chloride to the surface of a poly(2-vinylpyridine) particle which greatly decreased the cytotoxicity of cerium chloride to polymorphonuclear leukocytes and expands the choice of possible cultivation media This significantly improves the literature known staining protocols for the detection of ROS by transmission electron microscopy. The formation of ROS is indicated by the formation of a characteristic needle-like precipitate on the nanoparticles’ surface.