“It’s like sending disaster relief to a country far away but not really knowing how it gets there.”
Extracellular vesicles are the body’s text messages: little fat bubbles that carry vital information and cargo between cells.
However, we know little about how these messengers move about.
Australian Institute for Bioengineering and Nanotechnology (AIBN) researchers Amruta and Dr Dalila Ianotta say understanding this process could be key to developing new diagnostic and therapeutic approaches for diseases such as cancer.
Says Amruta: “We have little information about EVs move. It’s like preparing a package to leave our shores – and then only paying attention when it arrives at the final destination.
“How did it get there though? Did it go by boat? By plane? It’s probably a good thing to know!
“And you might say that it matters little, especially if the package ends up where it is meant to. But better knowledge of the process helps us with planning, it helps us maximise effectiveness, and it helps us with costs.
“That’s kind of where we are at the moment with EVs.”
In Nature Nanotechnology, Dalila, Amruta, and AIBN colleagues Dr Amanda Kijas, Professor Alan Rowan, and Associate Professor Joy Wolfram get to the core of the issue by discussing the potential nanoscale processes that EVs use to enter and exit the blood circulation.
The paper also summarises how the exponential growth of the EV field – and the accelerated pace at which emerging therapeutic and diagnostic EV-based products are being developed – highlight the pressing need to understand EV transport.
Potential pathways of EV entry to and exit from the blood circulation
a, General representation of endothelium types. It is worth noting that several types of endothelia can be found in some organs, such as the kidneys. b, Extracellular vesicles may cross the endothelial barrier through transcellular or paracellular transport routes. In the case of paracellular transport, EVs may pass through gaps between endothelial cells, which is likely to be a prominent transport route in organs with discontinuous vasculature, such as the liver. Extracellular vesicles may also modify interendothelial junctions to enable paracellular transport. In the case of transcellular transport, EVs may pass through intra-endothelial fenestrations or use various transcytosis pathways. Binding to lipoproteins to hijack caveolae-mediated transcytosis may also be exploited. Exocytosis-independent mechanisms of transcellular transport are also plausible, resulting in multilayered EVs released through membrane budding. Finally, cell protrusions can potentially be exploited as an alternative route for EV transport across the endothelial barrier.
Amruta says it could be argued that EV transport phenomena are the most critical component of a desired function, as an incorrect spatial context is futile and potentially detrimental.
“If we are going to use EVs as one of the components in our drug delivery systems, we need to know what the best way is we can administer them,” she says.
“Different methods will lead to different ways of these drug delivery systems being absorbed into the body. And if we don’t know how EVs are interacting or behaving within the body, or how they’re entering or leaving the bloodstream, it is pointless to administer them.
“Because then you’re just playing roulette. You’re just like “we’ll see”.
“So, that’s why we were keen on figuring out how exactly this process works: so that you’re not wasting time, energy, money, all of that, just to like have it all be unknown at the very end.”