Advanced Science,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 25, 2024
Abstract
Lipid
Nanoparticles
(LNPs)
recently
emerged
as
an
invaluable
RNA
delivery
platform.
With
many
LNP‐based
therapeutics
in
the
pre‐clinical
and
clinical
pipelines,
there
is
extensive
research
dedicated
to
improving
LNPs.
These
efforts
focus
mainly
on
tolerability
transfectability
of
new
ionizable
lipids
RNAs,
or
modulating
LNPs
biodistribution
with
active
targeting
strategies.
However,
most
formulations
follow
well‐established
lipid
proportions
used
clinically
approved
products.
Nevertheless,
investigating
effects
composition
their
can
expand
toolbox
for
particle
design,
leading
improved
Herein,
a
(30‐n‐LNPs)
formulation
increasing
amounts
phospholipids
investigated
possible
mRNA
system
treating
Inflammatory
Bowel
Diseases.
Compared
benchmark
(b‐LNPs),
n‐LNPs
containing
30%
distearoylphosphatidylcholine
(DSPC)
are
well
tolerated
following
intravenous
administration
display
natural
toward
inflamed
colon
dextran
sodium
sulfate
(DSS)‐colitis
bearing
mice,
while
de‐targeting
clearing
organs
such
liver
spleen.
Using
interleukin‐10‐encoding
therapeutic
cargo,
demonstrated
reduction
pathological
burden
colitis‐bearing
mice.
represent
starting
point
further
investigate
influence
systemic
biodistribution,
ultimately
opening
modalities
different
pathologies.
Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(11)
Опубликована: Март 4, 2024
Carriers
for
RNA
delivery
must
be
dynamic,
first
stabilizing
and
protecting
therapeutic
during
to
the
target
tissue
across
cellular
membrane
barriers
then
releasing
cargo
in
bioactive
form.
The
chemical
space
of
carriers
ranges
from
small
cationic
lipids
applied
lipoplexes
lipid
nanoparticles,
over
medium-sized
sequence-defined
xenopeptides,
macromolecular
polycations
polyplexes
polymer
micelles.
This
perspective
highlights
discovery
distinct
virus-inspired
dynamic
processes
that
capitalize
on
mutual
nanoparticle–host
interactions
achieve
potent
delivery.
From
host
side,
subtle
alterations
pH,
ion
concentration,
redox
potential,
presence
specific
proteins,
receptors,
or
enzymes
are
cues,
which
recognized
by
nanocarrier
via
designs
including
cleavable
bonds,
alterable
physicochemical
properties,
supramolecular
assembly–disassembly
respond
changing
biological
microenvironment
ACS Applied Materials & Interfaces,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 9, 2025
The
emergence
of
mRNA
vaccines
offers
great
promise
and
a
potent
platform
in
combating
various
diseases,
notably
COVID-19.
Nevertheless,
challenges
such
as
inherent
instability
potential
side
effects
current
delivery
systems
underscore
the
critical
need
for
advancement
stable,
safe,
efficacious
vaccines.
In
this
study,
robust
vaccine
(cmRNA-1130)
eliciting
immune
activation
has
been
developed
from
biodegradable
lipid
with
eight
ester
bonds
branched
tail
(AX4)
synthetic
circular
(cmRNA)
encoding
trimeric
Delta
receptor
binding
domain
SARS-CoV-2
spike
protein.
Notably,
cmRNA-1130
exhibits
outstanding
stability,
remaining
effective
after
six
months
storage
at
4
°C
multiple
freeze–thaw
cycles.
comparison
commercial
MC3
lipid,
nanoparticles
formed
degradable
AX4
revealed
much
faster
metabolic
rate
liver
spleen,
affording
negligible
impairment
to
hepatorenal
function.
Following
intramuscular
administration,
generates
sustained
neutralizing
antibodies
induces
RBD-specific
CD4+
CD8+
T
effector
memory
cells
(TEM)
Th1-biased
mice.
Featured
activation,
high
decent
safety,
cmRNA
hold
huge
clinical
prophylaxis
treatment
different
diseases.
Human Gene Therapy,
Год журнала:
2024,
Номер
35(17-18), С. 617 - 627
Опубликована: Авг. 14, 2024
Lipid
nanoparticles
(LNPs)
are
the
most
clinically
advanced
drug
delivery
system
for
nucleic
acid
therapeutics,
exemplified
by
success
of
COVID-19
mRNA
vaccines.
However,
their
clinical
use
is
currently
limited
to
hepatic
diseases
and
vaccines
due
tendency
accumulate
in
liver
upon
intravenous
administration.
To
fully
leverage
potential,
it
essential
understand
address
tropism,
while
also
developing
strategies
enhance
tissues
beyond
liver.
Ensuring
that
these
therapeutics
reach
target
cells
avoiding
off-target
both
efficacy
safety.
There
three
potential
targeting
strategies-passive,
active,
endogenous-which
can
be
used
individually
or
combination
nonhepatic
tissues.
In
this
review,
we
delve
into
recent
advancements
LNP
engineering
delivering