Cubic Phase‐Inducible Zwitterionic Phospholipids Improve the Functional Delivery of mRNA
Kazuki Iwakawa,
Rikako Sato,
Mariko Konaka
и другие.
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 17, 2025
Abstract
Lipid
nanoparticles
(LNPs)
are
clinically
advanced
delivery
systems
for
RNA.
The
extensively
developed
structure
of
ionizable
lipids
greatly
contributes
to
the
functional
mRNA.
However,
endosomal
escape
is
one
severe
biological
barriers
that
continue
render
this
process
inefficient
(e.g.,
less
than
10%).
Although
LNPs
contain
phospholipids,
their
role
poorly
understood,
and
there
have
been
few
attempts
perform
chemical
engineering
required
improve
functionality.
Herein,
a
cubic
phase‐inducible
fusogenic
zwitterionic
phospholipid
derived
from
1,2‐dioleoyl‐3‐
sn
‐glycero‐phosphoethanolamine
(DOPE),
DOPE‐Cx
described,
designed
correct
problem.
orientation
head
group
DOPE
engineered
by
attaching
series
hydrophobic
moieties
intermolecular
interaction
with
phosphatidylcholine
(PC),
followed
lipid‐phase
transition
into
non‐lamellar
phases
facilitate
membrane
fusion‐mediated
escape.
A
structure–activity
relationship
study
reveals
small
chains
induce
instead
hexagonal
phase
when
mixed
PC,
which
enhances
mRNA
in
liver
as
opposed
action
typically
utilized
naturally
occurring
phospholipids.
Engineered
functionalized
phospholipids
will
be
great
value
therapeutic
applications
mRNAs.
Язык: Английский
Advanced microfluidic strategies for core-shell nanoparticles: the next-generation of polymeric and lipid-based drug nanocarriers
Chemical Engineering Journal Advances,
Год журнала:
2025,
Номер
unknown, С. 100759 - 100759
Опубликована: Апрель 1, 2025
Язык: Английский
Elucidating the uptake and trafficking of nanostructured lipid carriers as delivery systems for miRNA
European Journal of Pharmaceutical Sciences,
Год журнала:
2024,
Номер
unknown, С. 106973 - 106973
Опубликована: Ноя. 1, 2024
Cationic
nanostructured
lipid
carriers
(cNLCs)
represent
promising
non-viral
for
nucleic
acids,
such
as
miRNAs,
forming
stable
self-assembled
miRNA
complexes
due
to
electrostatic
interactions.
Prepared
by
high-pressure
homogenization,
cNLC
formulations,
both
with
and
without
Nile
Red
dye
demonstrated
particle
sizes
in
the
range
of
100-120
nm
positive
surface
charges
(>
30
mV),
which
are
necessary
effective
cellular
uptake.
The
formed
at
mass
ratios
1:2.5
1:5
showed
similar
stability
size,
zeta
potentials,
well
high
cell
viability
80%)
3T3-L1
MCF-7
lines.
uptake
studies
miRNA:cNLC
lines
revealed
that
was
time-
concentration-dependent,
rapid
initial
minutes
a
zig-zag
pattern
over
24
hours.
To
elucidate
endocytosis
mechanism
complexes,
cells
were
incubated
different
inhibitors
(chlorpromazine,
5-[N-ethyl-N-isopropyl]
amiloride,
dynasore,
nystatin,
or
sodium
azide
2-deoxy-D-glucose).
Results
significant
inhibition
low
temperatures
ATP
depletion,
suggesting
endocytosis,
particularly
macropinocytosis,
main
cells.
In
cells,
less
inhibited
substances,
indicating
need
more
specific
methods
fully
decipher
endocytic
mechanisms
involved.
Confocal
laser
scanning
microscopy
images
internalized
vesicles,
primarily
localized
juxtanuclear
region,
trafficking
through
endolysosomal
system.
Colocalization
study
LysoTracker™
Green
DND-26
colocalization
lysosomes
lower,
macropinocytosis
primary
mechanism.
Additional
partial
between
labeled
NLCs
miRNA,
about
50%
is
released
from
within
post-transfection.
Язык: Английский
Attempts to preserve and visualize protein corona on the surface of biological nanoparticles in blood serum using photomodification
Beilstein Journal of Nanotechnology,
Год журнала:
2024,
Номер
15, С. 1654 - 1666
Опубликована: Дек. 30, 2024
A
protein
corona
is
present
on
any
nanoparticle
(NP)
entering
biological
fluids;
however,
the
existence
of
a
natural
NPs
has
not
been
experimentally
confirmed.
We
used
our
previously
developed
photomodification
method
to
fix
“biological
nanoparticles”
(bio-NPs)
in
fetal
bovine
serum
and
newborn
serum;
native
sera
served
as
control.
To
isolate
photomodified
bio-NPs,
we
ultracentrifugation
(UC),
sucrose
gradient
(12%,
30%,
50%),
cushion
(30%)
methods.
Isolated
bio-NPs
were
visualized
using
transmission
electron
microscopy.
The
results
showed
that
extracellular
vesicles
lipoproteins
isolated
by
UC.
isolation
through
or
did
preserve
corona.
At
same
time,
observed
signs
negative
effect
intact
when
isolating
these
particles
cushion,
no
effects
observed.
believe
data
will
be
useful
researchers
solutions
working
properties
In
this
work,
have
obtained
direct
images
“natural”
blood
for
first
time
Язык: Английский