间充质干细胞
体内
细胞生物学
小泡
生物物理学
肝星状细胞
化学
免疫系统
白蛋白
干细胞
生物
免疫学
生物化学
膜
内分泌学
生物技术
作者
Revadee Liam‐Or,Farid N. Faruqu,Adam A. Walters,Shunping Han,Lizhou Xu,Julie Wang,Jennifer Oberlaender,Alberto Sánchez‐Fueyo,Giovanna Lombardi,Francesco Dazzi,Volker Mailänder,Khuloud T. Al‐Jamal
标识
DOI:10.1038/s41565-023-01585-y
摘要
Abstract 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.
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