Grant: Travel Awards - Institute Community Support

Extracellular vesicles (EVs) are tiny particles released by cells that help them communicate by transferring proteins and other molecules. These particles play a role in processes like cancer spread, but their complexity and production challenges make them difficult to study. To overcome this, we designed synthetic extracellular vesicles (SVs) that mimic the structural properties of natural EVs. These SVs allow us to incorporate specific proteins to study their impact on SV behavior and interactions with recipient cells. We isolated natural EVs from cancer cells to understand their properties, such as size, charge, and protein content, and used this information to create synthetic versions. As a proof of concept, proteins from the cell membrane and the inside of cells were loaded separately or together into the SVs. Using advanced tools like mass spectrometry and fluorescence microscopy, we studied protein incorporation efficiency and cellular internationalization. Our SVs were produced efficiently, mimicking the size of natural EVs. The surface charge of SVs was similar to that of natural EVs when membrane proteins were included. Interestingly, proteins with specific characteristics, such as smaller size and higher electric charge, were more likely to be incorporated into the SVs. We found that SVs with membrane proteins were taken up by cells more efficiently than those without. When injected into mice, these SVs accumulated in specific organs, such as the liver and spleen, similar to natural EVs. Further analysis revealed that SVs were taken up by specific cells in the liver, such as Kupffer cells, showing their cell type -specific interactions within the body. This research demonstrates that SVs can be customized to study the role of individual proteins in cell communication. These findings may improve our understanding of EV biology and support the development of targeted drug delivery systems for diseases like cancer.