Electron tomography in nanoparticle imaging and analysis

A wide range of medically important nanosized biological assemblies are not amenable to study by standard structural techniques, such as x-ray crystallography or nuclear magnetic resonance spectroscopy, either owing to their large size or the intrinsic heterogeneity of the specimen. The emerging technique of cryo-electron tomography is being applied actively to study these nanoparticles and has the potential of providing high-resolution structural information on these heterogeneous assemblies. Although the majority of structural methods involve the averaging of large numbers of structurally homogeneous molecules, tomography enables the visualization and quantitation of variation in a mixed population. Here, we present a review of the principles of cryo-electron tomography as applied to the 3D analysis of nanoparticles and illustrate applications where it can be used for visualizing the architecture of enveloped viruses and for the analysis of size and compositional variation of Doxil, a commonly used, US FDA-approved nanomedicine.