Rapid detection of intracellular nanoparticles by electron microscopy

Recently, a number of nanoparticle carriers have provided new platforms for research in biotechnology and biomedicine. A particularly interest in these fields is the monitoring of nanoparticle delivery to target cells. Since the structures involved are on a nanometer scale, high resolution imaging, such as electron microscopy, is required. Aside from assessing the structural characteristics of the target sites localized with the nanoparticles, an electron microscope can also be used to observe the biological effects of the nanoparticles on the cells. It can also be used to test and detect a wide range of fluorescent nanoparticles and nanoassemblies. Although this approach has many advantages, most researchers are unwilling to try electron microscopy due to the complicated specimen preparation procedures and time-consuming process. Here, we developed a method to simplify the sample preparation and shorten the total processing time. In particular, double staining was removed, and cryo-preparation was included. Using this simple and rapid sample preparation, we were able to observe nanoparticles with high-contrast images of the cellular organelles. This efficient detection method can be applied to studies on nanoparticle drug delivery systems and nanoparticle-cell interactions.