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 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.