TY - JOUR
T1 - Cellular uptake and in vivo distribution of mesenchymal-stem-cell-derived extracellular vesicles are protein corona dependent
AU - Liam-Or, Revadee
AU - Faruqu, Farid N.
AU - Walters, Adam
AU - Han, Shunping
AU - Xu, Lizhou
AU - Wang, Julie Tzu Wen
AU - Oberlaender, Jennifer
AU - Sanchez-Fueyo, Alberto
AU - Lombardi, Giovanna
AU - Dazzi, Francesco
AU - Mailaender, Volker
AU - Al-Jamal, Khuloud T.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/6
Y1 - 2024/6
N2 - Extracellular vesicles (EVs) derived from mesenchymal stem cells are promising nanotherapeutics in liver diseases due to their regenerative and immunomodulatory properties. Nevertheless, a concern has been raised regarding the rapid clearance of exogenous EVs by phagocytic cells. Here we explore the impact of protein corona on EVs derived from two culturing conditions in which specific proteins acquired from media were simultaneously adsorbed on the EV surface. Additionally, by incubating EVs with serum, simulating protein corona formation upon systemic delivery, further resolved protein corona–EV complex patterns were investigated. Our findings reveal the potential influences of corona composition on EVs under in vitro conditions and their in vivo kinetics. Our data suggest that bound albumin creates an EV signature that can retarget EVs from hepatic macrophages. This results in markedly improved cellular uptake by hepatocytes, liver sinusoidal endothelial cells and hepatic stellate cells. This phenomenon can be applied as a camouflage strategy by precoating EVs with albumin to fabricate the albumin-enriched protein corona–EV complex, enhancing non-phagocytic uptake in the liver. This work addresses a critical challenge facing intravenously administered EVs for liver therapy by tailoring the protein corona–EV complex for liver cell targeting and immune evasion.
AB - Extracellular vesicles (EVs) derived from mesenchymal stem cells are promising nanotherapeutics in liver diseases due to their regenerative and immunomodulatory properties. Nevertheless, a concern has been raised regarding the rapid clearance of exogenous EVs by phagocytic cells. Here we explore the impact of protein corona on EVs derived from two culturing conditions in which specific proteins acquired from media were simultaneously adsorbed on the EV surface. Additionally, by incubating EVs with serum, simulating protein corona formation upon systemic delivery, further resolved protein corona–EV complex patterns were investigated. Our findings reveal the potential influences of corona composition on EVs under in vitro conditions and their in vivo kinetics. Our data suggest that bound albumin creates an EV signature that can retarget EVs from hepatic macrophages. This results in markedly improved cellular uptake by hepatocytes, liver sinusoidal endothelial cells and hepatic stellate cells. This phenomenon can be applied as a camouflage strategy by precoating EVs with albumin to fabricate the albumin-enriched protein corona–EV complex, enhancing non-phagocytic uptake in the liver. This work addresses a critical challenge facing intravenously administered EVs for liver therapy by tailoring the protein corona–EV complex for liver cell targeting and immune evasion.
UR - http://www.scopus.com/inward/record.url?scp=85185147674&partnerID=8YFLogxK
U2 - 10.1038/s41565-023-01585-y
DO - 10.1038/s41565-023-01585-y
M3 - Article
C2 - 38366223
AN - SCOPUS:85185147674
SN - 1748-3387
VL - 19
SP - 846
EP - 855
JO - Nature Nanotechnology
JF - Nature Nanotechnology
IS - 6
ER -