ABSTRACT
Exosomes are stable nanovesicles secreted by cells into the circulation. Their reported sizes differ substantially, which likely reflects the difference in the isolation techniques used, the cells that secreted them, and the methods used in their characterization. We analyzed the influence of the last factor on the measured sizes and shapes of hydrated and desiccated exosomes isolated from the serum of a pancreatic cancer patient and a healthy control. We found that hydrated exosomes are close-to-spherical nanoparticles with a hydrodynamic radius that is substantially larger than the geometric size. For desiccated exosomes, we found that the desiccated shape and sizing are influenced by the manner in which drying occurred. Isotropic desiccation in aerosol preserves the near-spherical shape of the exosomes, whereas drying on a surface likely distorts their shapes and influences the sizing results obtained by techniques that require surface fixation prior to analysis.
Subject(s)
Cytological Techniques/methods , Exosomes/chemistry , Adult , Aged , Cryoelectron Microscopy , Desiccation , Dynamic Light Scattering , Female , Humans , Microscopy, Electron, Scanning , Models, TheoreticalABSTRACT
Nanoscale characterization tools hold the potential to overcome long-standing medicinal and pharmaceutical challenges. For example, electrospray differential mobility analysis (ES-DMA) is an emerging tool that rapidly provides label-free multimodal size distributions for proteins and particles from ~1 nm to <500 nm with subnanometer precision. Here we critically review the contributions of this tool to medicine, pharmaceutical practice, and pharmaceutical production. Our review critically evaluates, first, the use of ES-DMA for diagnostic strategies that detect and quantify lipoproteins, bacterial infections, viruses and amyloid fibrillation and then focuses on ES-DMA's contribution to treatment strategies that employ tailored virus-like particles as vaccines and decorated nanoparticle vectors for gene delivery. Our review also highlights ES-DMA's contribution to viral clearance and antibody aggregation and potential as a process analytical technology (PAT). FROM THE CLINICAL EDITOR: Electrospray differential mobility analysis is an emerging nanotechnology-based tool with potential clinical utility in the detection and quantification of lipoproteins, glycoproteins, viruses, amyloids, bacterial infections. Its contribution to treatment strategies and pharmaceutical production is also discussed in this comprehensive review.
