Development and Characterization of Bioinspired Lipid Raft Nanovesicles for Therapeutic Applications

Lipid rafts are highly ordered regions of the plasma membrane enriched in signaling proteins and lipids. Their biological potential is realized in exosomes, a subclass of extracellular vesicles (EVs) that originate from the lipid raft domains. Previous studies have shown that EVs derived from human...

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Bibliographic Details
Published in:ACS applied materials & interfaces 2022-12, Vol.14 (49), p.54458-54477
Main Authors: Ramasubramanian, Lalithasri, Jyothi, Harsha, Goldbloom-Helzner, Leora, Light, Brandon M., Kumar, Priyadarsini, Carney, Randy P., Farmer, Diana L., Wang, Aijun
Format: Article
Language:English
Subjects:
Biological and Medical Applications of Materials and Interfaces
Cell Membrane - metabolism
Female
Humans
Lipids
Membrane Microdomains
Placenta
Pregnancy
Proteins - metabolism
Proteomics
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Summary:Lipid rafts are highly ordered regions of the plasma membrane enriched in signaling proteins and lipids. Their biological potential is realized in exosomes, a subclass of extracellular vesicles (EVs) that originate from the lipid raft domains. Previous studies have shown that EVs derived from human placental mesenchymal stromal cells (PMSCs) possess strong neuroprotective and angiogenic properties. However, clinical translation of EVs is challenged by very low, impure, and heterogeneous yields. Therefore, in this study, lipid rafts are validated as a functional biomaterial that can recapitulate the exosomal membrane and then be synthesized into biomimetic nanovesicles. Lipidomic and proteomic analyses show that lipid raft isolates retain functional lipids and proteins comparable to PMSC-EV membranes. PMSC-derived lipid raft nanovesicles (LRNVs) are then synthesized at high yields using a facile, extrusion-based methodology. Evaluation of biological properties reveals that LRNVs can promote neurogenesis and angiogenesis through modulation of lipid raft-dependent signaling pathways. A proof-of-concept methodology further shows that LRNVs could be loaded with proteins or other bioactive cargo for greater disease-specific functionalities, thus presenting a novel type of biomimetic nanovesicles that can be leveraged as targeted therapeutics for regenerative medicine.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.2c13868