Single Nanovesicles Tracking Reveals Their Heterogeneous Extracellular Adsorptions

The vigorous nanomedicine offers significant possibilities for effective therapeutics of various diseases, and nanovesicles (NVs) represented by artificial liposomes and natural exosomes and cytomembranes especially show great potential. However, their complex interactions with cells, particularly the heterogeneous extracellular adsorptions, are difficult to analyze spatiotemporally due to the transient dynamics. In this study, by single NVs tracking, the extracellular NVs adsorptions are directly observed and their heterogeneous characteristics are revealed. Briefly, plenty of NVs adsorbed on HCT116 cells are tracked and classified, and it is discovered that they exhibit various diffusion properties from different extracellular regions: stable adsorptions on the rear surface and restricted adsorptions on the front protrusion. After the hydrolysis of hyaluronic acid in the extracellular matrix by hyaluronidase, the restricted adsorptions are further weakened and manifested as dissociative adsorptions, which demonstrated reduced total NVs adsorptions from a single-cell and single-particle perspective. Compared with traditional static analysis, the spatiotemporal tracking and heterogeneous results not only reveal the extracellular NVs-cell interactions but also inspire a wide variety of nanomedicine and their nano-investigations.