학술논문
Cellular uptake and in vivo distribution of mesenchymal-stem-cell-derived extracellular vesicles are protein corona dependent.
Document Type
Academic Journal
Author
Liam-Or R; Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, London, UK.; Faruqu FN; Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, London, UK.; Pharmacology Department, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.; Walters A; Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, London, UK.; Han S; Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, London, UK.; Xu L; Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, London, UK.; Wang JT; Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, London, UK.; Oberlaender J; Max Planck Institute for Polymer Research, Mainz, Germany.; Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.; Sanchez-Fueyo A; Institute of Liver Studies, King's College London University and King's College Hospital, London, UK.; Lombardi G; Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK.; Dazzi F; Comprehensive Cancer Centre, King's College London, London, UK.; Mailaender V; Max Planck Institute for Polymer Research, Mainz, Germany.; Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.; Al-Jamal KT; Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, London, UK. khuloud.al-jamal@kcl.ac.uk.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101283273 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1748-3395 (Electronic) Linking ISSN: 17483387 NLM ISO Abbreviation: Nat Nanotechnol Subsets: MEDLINE
Subject
Language
English
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.
(© 2024. The Author(s).)
(© 2024. The Author(s).)