Extracellular vesicles

Extracellular Vesicles (shortened as EV's) are sub-micron sized particles which have an enclosing membrane. They are one mechanism for inter-cellular communication. They are composed of lipids and proteins, and there may be nucleic acid inside (the cargo)[@libregts2018Flow cytometric analysis of extracellular vesicle subsets in plasma: impact of swarm by particles of non-interest].

Extracellular vesicles were initially called nanovesicles, and they belong to one of three different categories based on their biogenesis [[literature/@pedrioli2021|@pedrioli2021]] [[literature/@elsharkasy2020|@elsharkasy2020]]:

• Apoptotic Bodies (ApoBDs)
• Microvesicles (MV)
• Exosomes (EXO)

There is a possibility of using exosomes as drug delivery systems since they are biocompatible, and already have a similar natural role in multicellular organisms.

Another alternative is using EVs as biomarkers, since it is believed that the regulation of the release and composition of these particles can be correlated to certain diseases.

The biggest challenge is that most exosomes and microvesicles are $<500\textrm{nm}$ in diameter, and therefore hard to detect by standard instruments:

• Limitations of NTA for Extracellular Vesicles measurements
• Limitations of Flow Cytometry for Extracellular Vesicles measurements
• Limitations of TRPS for Extracellular Vesicles measurements
• Limitations of A4F-DLS-MALS

Moreover, detecting rare particles (perhaps 1% of the particles change between healthy and non healthy humans). This is why detecting Low abundance EVs may be crucial in the future.

Techniques such as Simoa, SP-IRIS, or Multiplex bead-based flow cytometry can be useful tools to detect rare events. Perhaps the EVQuant protocol is also relevant in these contexts.