Abstract:Stabilizer P80 concentrated to lipid liquid crystalline particle surface, but contributes also to the inner sponge phase structure. Particles spread on surfaces to form bilayers.
“…Finally, from the broad peak position in samples MCH and MCHPC, an internal d -spacing of 6.35 ± 0.02 nm is found. This distance probably represents the characteristic d -spacing of the inverse worm-like micellar structure of the core. , This is consistent with previous results obtained on bulk phase samples …”
Section: Resultssupporting
confidence: 92%
“…The SANS data in Figure A–C were analyzed using either a simultaneous fit for the core–shell sphere model only (sample MMC) or adding a broad peak model to better describe the data in the q range above 0.05 Å –1 (samples MCH and MCHPC). A detailed description of the data analysis can be found in the Supporting Information (SI).…”
Emerging
therapeutic treatments based on the production of proteins
by delivering mRNA have become increasingly important in recent times.
While lipid nanoparticles (LNPs) are approved vehicles for small interfering
RNA delivery, there are still challenges to use this formulation for
mRNA delivery. LNPs are typically a mixture of a cationic lipid, distearoylphosphatidylcholine
(DSPC), cholesterol, and a PEG-lipid. The structural characterization
of mRNA-containing LNPs (mRNA-LNPs) is crucial for a full understanding
of the way in which they function, but this information alone is not
enough to predict their fate upon entering the bloodstream. The biodistribution
and cellular uptake of LNPs are affected by their surface composition
as well as by the extracellular proteins present at the site of LNP
administration, e.g., apolipoproteinE (ApoE). ApoE,
being responsible for fat transport in the body, plays a key role
in the LNP’s plasma circulation time. In this work, we use
small-angle neutron scattering, together with selective lipid, cholesterol,
and solvent deuteration, to elucidate the structure of the LNP and
the distribution of the lipid components in the absence and the presence
of ApoE. While DSPC and cholesterol are found to be enriched at the
surface of the LNPs in buffer, binding of ApoE induces a redistribution
of the lipids at the shell and the core, which also impacts the LNP
internal structure, causing release of mRNA. The rearrangement of
LNP components upon ApoE incubation is discussed in terms of potential
relevance to LNP endosomal escape.
“…Finally, from the broad peak position in samples MCH and MCHPC, an internal d -spacing of 6.35 ± 0.02 nm is found. This distance probably represents the characteristic d -spacing of the inverse worm-like micellar structure of the core. , This is consistent with previous results obtained on bulk phase samples …”
Section: Resultssupporting
confidence: 92%
“…The SANS data in Figure A–C were analyzed using either a simultaneous fit for the core–shell sphere model only (sample MMC) or adding a broad peak model to better describe the data in the q range above 0.05 Å –1 (samples MCH and MCHPC). A detailed description of the data analysis can be found in the Supporting Information (SI).…”
Emerging
therapeutic treatments based on the production of proteins
by delivering mRNA have become increasingly important in recent times.
While lipid nanoparticles (LNPs) are approved vehicles for small interfering
RNA delivery, there are still challenges to use this formulation for
mRNA delivery. LNPs are typically a mixture of a cationic lipid, distearoylphosphatidylcholine
(DSPC), cholesterol, and a PEG-lipid. The structural characterization
of mRNA-containing LNPs (mRNA-LNPs) is crucial for a full understanding
of the way in which they function, but this information alone is not
enough to predict their fate upon entering the bloodstream. The biodistribution
and cellular uptake of LNPs are affected by their surface composition
as well as by the extracellular proteins present at the site of LNP
administration, e.g., apolipoproteinE (ApoE). ApoE,
being responsible for fat transport in the body, plays a key role
in the LNP’s plasma circulation time. In this work, we use
small-angle neutron scattering, together with selective lipid, cholesterol,
and solvent deuteration, to elucidate the structure of the LNP and
the distribution of the lipid components in the absence and the presence
of ApoE. While DSPC and cholesterol are found to be enriched at the
surface of the LNPs in buffer, binding of ApoE induces a redistribution
of the lipids at the shell and the core, which also impacts the LNP
internal structure, causing release of mRNA. The rearrangement of
LNP components upon ApoE incubation is discussed in terms of potential
relevance to LNP endosomal escape.
“…We further characterized the droplets by cryogenic transmission electron microscopy (cryo-TEM) and found that they lack any well-ordered internal structure, consistent with the characteristics of a sponge phase (SI Appendix, Fig. S6A) (30). Deviation from spherical shape is observed likely because of the mechanical stress inherent in the cryo-TEM sample preparation method.…”
Living cells segregate molecules and reactions in various subcellular compartments known as organelles. Spatial organization is likely essential for expanding the biochemical functions of synthetic reaction systems, including artificial cells. Many studies have attempted to mimic organelle functions using lamellar membrane-bound vesicles. However, vesicles typically suffer from highly limited transport across the membranes and an inability to mimic the dense membrane networks typically found in organelles such as the endoplasmic reticulum. Here, we describe programmable synthetic organelles based on highly stable nonlamellar sponge phase droplets that spontaneously assemble from a single-chain galactolipid and nonionic detergents. Due to their nanoporous structure, lipid sponge droplets readily exchange materials with the surrounding environment. In addition, the sponge phase contains a dense network of lipid bilayers and nanometric aqueous channels, which allows different classes of molecules to partition based on their size, polarity, and specific binding motifs. The sequestration of biologically relevant macromolecules can be programmed by the addition of suitably functionalized amphiphiles to the droplets. We demonstrate that droplets can harbor functional soluble and transmembrane proteins, allowing for the colocalization and concentration of enzymes and substrates to enhance reaction rates. Droplets protect bound proteins from proteases, and these interactions can be engineered to be reversible and optically controlled. Our results show that lipid sponge droplets permit the facile integration of membrane-rich environments and self-assembling spatial organization with biochemical reaction systems.
“…6c, the plot of dissipation versus frequency revealed a kink for 1% DOTAP cubosomes, which may suggest the rearrangement of lipid material. 51 Fig. 6Surface measurements during cubosome uptake measured by QCM-D. a Shift in frequency normalised by overtone (ΔF/ n ) with time.…”
Drug delivery with nanocarriers relies on the interaction of individual nanocarriers with the cell surface. For lipid-based NCs, this interaction uniquely involves a process of membrane fusion between the lipid bilayer that makes up the NC and the cell membrane. Cubosomes have emerged as promising fusogenic NCs, however their individual interactions had not yet been directly observed due to difficulties in achieving adequate resolution or disentangling multiple interactions with common characterization techniques. Moreover, many studies on these interactions have been performed under static conditions which may not mimic the actual transport of NCs. Herein we have observed fusion of lipid cubosome NCs with lipid bilayers under flow. Total internal reflection microscopy has allowed visualisation of the fusion event which was sensitive to the lipid compositions and rationalized by lipid diffusion. The fusion event in supported lipid bilayers has been compared with those in cells, revealing a distinct similarity in kinetics.
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