Bioconjugate Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 20, 2024
mRNA
lipid
nanoparticles
(LNPs)
are
a
powerful
technology
that
actively
being
investigated
for
their
ability
to
prevent,
treat,
and
study
disease.
However,
major
limitation
remains:
achieving
extrahepatic
expression.
The
development
of
new
carriers
could
enable
the
expression
in
non-liver
targets,
thus
expanding
utility
mRNA-based
medicines.
In
this
study,
we
use
combination
chemoinformatic-guided
material
synthesis
design
experiment
optimization
spleen-expressing
nanoparticle
(SE-LNP).
We
begin
with
novel
cholesterol
derivative
followed
by
SE-LNP
formulation
experiment-guided
identify
three
lead
SE-LNPs.
then
evaluate
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июль 5, 2024
Abstract
Fully
targeted
mRNA
therapeutics
necessitate
simultaneous
organ-specific
accumulation
and
effective
translation.
Despite
some
progress,
delivery
systems
are
still
unable
to
fully
achieve
this.
Here,
we
reformulate
lipid
nanoparticles
(LNPs)
through
adjustments
in
material
structures
compositions
systematically
the
pulmonary
hepatic
(respectively)
distribution
expression.
A
combinatorial
library
of
degradable-core
based
ionizable
cationic
lipids
is
designed,
following
by
optimisation
LNP
compositions.
Contrary
current
paradigms,
our
findings
demonstrate
that
cholesterol
phospholipid
dispensable
for
functionality.
Specifically,
cholesterol-removal
addresses
persistent
challenge
preventing
nanoparticle
tissues.
By
modulating
simplifying
intrinsic
components,
concurrent
translation
achieved
lung
liver,
respectively.
This
targeting
strategy
applicable
existing
with
potential
expand
progress
precise
therapy
diverse
diseases.
Vaccines,
Год журнала:
2024,
Номер
12(10), С. 1148 - 1148
Опубликована: Окт. 8, 2024
The
advent
of
lipid
nanoparticles
(LNPs)
as
a
delivery
platform
for
mRNA
therapeutics
has
revolutionized
the
biomedical
field,
particularly
in
treating
infectious
diseases,
cancer,
genetic
disorders,
and
metabolic
diseases.
Recent
Advances
Therapeutic
LNPs:
LNPs,
composed
ionizable
lipids,
phospholipids,
cholesterol,
polyethylene
glycol
(PEG)
facilitate
efficient
cellular
uptake
cytosolic
release
while
mitigating
degradation
by
nucleases.
However,
synthetic
entities,
LNPs
face
challenges
that
alter
their
therapeutic
efficacy
safety
concerns.
Toxicity/Reactogenicity/Immunogenicity:
This
review
provides
comprehensive
overview
latest
advancements
LNP
research,
focusing
on
preclinical
assessments
encompassing
toxicity,
reactogenicity,
immunogenicity.
Summary
Outlook:
Additionally,
it
outlines
potential
strategies
addressing
these
offers
insights
into
future
research
directions
enhancing
application
therapeutics.
Advanced Materials,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 9, 2025
Lipid
nanoparticles
(LNPs)
with
highly
efficient
and
specific
extrahepatic
targeting
abilities
are
promising
in
gene
delivery,
the
lipopeptides
(LPs)
excellent
designability
functionality
expected
to
empower
construction
of
functional
LNPs.
This
study
aims
develop
ionizable
components
that
accurately
match
different
lipid
systems
through
modular
design
LPs.
Based
on
this,
a
lipopeptide-based
organ-specific
(POST)
LNP
screening
strategy
is
constructed,
which
lysine-histidine-based
(KH-LPs)
designed
as
components.
The
optimal
KH-LP
screened
vitro
shows
siRNA/mRNA
transfecting
ability
various
hard-to-transfect
cell
lines.
Compared
classic
LNPs,
POST
LNPs
vivo
achieve
even
higher
(or
at
least
comparable)
efficiency
specificity
delivering
mRNA
siRNA
lung,
liver,
spleen,
respectively.
structure-activity
relationship
(SAR)
proves
regulation
LP
structures
can
provide
for
systems,
demonstrating
potential
this
developing
selective
open
up
more
possibilities
therapy.
Molecular Therapy — Methods & Clinical Development,
Год журнала:
2025,
Номер
33(1), С. 101436 - 101436
Опубликована: Фев. 16, 2025
Lipid
nanoparticles
(LNPs)
are
now
highly
effective
transporters
of
nucleic
acids
to
the
liver.
This
liver-specificity
is
largely
due
their
association
with
certain
serum
proteins,
most
notably
apolipoprotein
E
(ApoE),
which
directs
them
liver
cells
by
binding
low-density
lipoprotein
(LDL)
receptors
on
hepatocytes.
The
liver's
distinct
anatomy,
its
various
specialized
cell
types,
also
influences
how
LNPs
taken
up
from
circulation,
cleared,
and
they
in
delivering
treatments.
In
this
review,
we
consider
factors
that
facilitate
LNP's
targeting
explore
latest
advances
liver-targeted
LNP
technologies.
Understanding
targeted
can
help
for
design
optimization
nanoparticle-based
therapies.
Comprehension
cellular
interaction
biodistribution
not
only
leads
better
treatments
diseases
but
delivers
insight
directing
other
tissues,
potentially
broadening
range
therapeutic
applications.
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 18, 2025
Abstract
Targeted
delivery
of
mRNA
with
lipid
nanoparticles
(LNPs)
holds
great
potential
for
treating
pulmonary
diseases.
However,
the
lack
rational
design
principles
efficient
lung‐homing
lipids
hinders
prevalence
therapeutics
in
this
organ.
Herein,
combinatorial
screening
structure‐function
analysis
is
applied
to
rationalize
strategy
nonpermanently
charged
lung‐targeted
ionizable
lipids.
It
discovered
that
carrying
N‐methyl
and
secondary
amine
groups
heads,
three
tails
originated
from
epoxyalkanes,
exhibiting
superior
selectivity
efficiency.
Representative
systematically
variation
chemical
structures
are
selected
study
well‐known
but
still
puzzling
“protein
corona”
adsorbed
on
surface
LNPs.
In
addition
commonly
used
corona‐biomarker
vitronectin,
other
arginine‐glycine‐aspartic
acid
(RGD)‐rich
proteins
usually
involved
collagen‐containing
extracellular
matrix,
such
as
fibrinogen
fibronectin
have
also
been
identified
a
strong
correlation
lung
tropism.
This
work
provides
insight
into
lung‐targeting
reveals
previously
unreported
function
RGD‐rich
protein
corona
Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(11)
Опубликована: Март 4, 2024
Due
to
its
small
size
and
lifelong
optical
transparency,
the
fish
Danionella
cerebrum
is
an
emerging
model
organism
in
biomedical
research.
How
can
this
vertebrate
under
12
mm
length
produce
sounds
over
140
dB?
We
found
that
it
possesses
...Motion
basis
of
nearly
all
animal
behavior.
Evolution
has
led
some
extraordinary
specializations
propulsion
mechanisms
among
invertebrates,
including
mandibles
dracula
ant
claw
pistol
shrimp.
In
contrast,
...
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(21), С. 14785 - 14798
Опубликована: Май 14, 2024
Selective
RNA
delivery
is
required
for
the
broad
implementation
of
clinical
applications,
including
prophylactic
and
therapeutic
vaccinations,
immunotherapies
cancer,
genome
editing.
Current
polyanion
relies
heavily
on
cationic
amines,
while
guanidinium
systems
have
received
limited
attention
due
in
part
to
their
strong
association,
which
impedes
intracellular
release.
Here,
we
disclose
a
general
solution
this
problem
groups
are
used
form
stable
complexes
upon
formulation
but
at
physiological
pH
undergo
novel
charge-neutralization
process,
resulting
This
new
system
consists
guanidinylated
serinol
moieties
incorporated
into
charge-altering
releasable
transporter
(GSer-CARTs).
Significantly,
systematic
variations
structure
resulted
GSer-CARTs
that
exhibit
highly
selective
mRNA
lung
(∼97%)
spleen
(∼98%)
without
targeting
ligands.
Illustrative
breadth
translational
potential,
deliver
circRNA,
providing
basis
cancer
vaccination
strategy,
murine
model
antigen-specific
immune
responses
effective
suppression
established
tumors.
