International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: 672, P. 125297 - 125297
Published: Feb. 1, 2025
Language: Английский
Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(4), P. 281 - 300
Published: Jan. 23, 2024
Language: Английский
Citations
66
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: Feb. 12, 2024
Abstract Efficient cytosolic delivery of RNA molecules remains a formidable barrier for therapeutic strategies. Lipid nanoparticles (LNPs) serve as state-of-the-art carriers that can deliver intracellularly, exemplified by the recent implementation several vaccines against SARS-CoV-2. Using bottom-up rational design approach, we assemble LNPs contain programmable lipid phases encapsulating small interfering (siRNA). A combination cryogenic transmission electron microscopy, tomography and small-angle X-ray scattering reveals form inverse hexagonal structures, which are present in liquid crystalline nature within LNP core. Comparison with lamellar presence enhances intracellular silencing efficiency over structures. We then demonstrate exhibit an situ transition from to phase upon interaction anionic membranes, whereas containing pre-programmed bypass this more efficient one-step mechanism, explaining increased effect. This defined structures aids understanding nano-bio interface adds substantial value design, optimization use.
Language: Английский
Citations
31
Journal of Colloid and Interface Science, Journal Year: 2024, Volume and Issue: 660, P. 66 - 76
Published: Jan. 5, 2024
The
development
of
lipid
nanoparticle
(LNP)
based
therapeutics
for
delivery
RNA
has
triggered
the
advance
new
strategies
formulation,
such
as
high
throughput
microfluidics
precise
mixing
components
into
well-defined
particles.
In
this
study,
we
have
characterised
structure
LNPs
throughout
formulation
process
using
in
situ
small
angle
x-ray
scattering
microfluidic
chip,
then
by
sampling
subsequent
dialysis
process.
final
was
investigated
with
(SAXS)
and
neutron
(SANS)
scattering,
dynamic
light
(DLS)
cryo-TEM.
effect
on
a
benchmark
composition
containing
different
cargos:
calf
thymus
DNA
(DNA)
two
model
mRNAs,
polyadenylic
acid
(polyA)
polyuridylic
(polyU).
LNP
evolved
during
channel,
however
only
fully
developed
dialysis.
colloidal
stability
affected
type
incorporated
nucleic
acids
(NAs)
decreased
degree
base-pairing,
polyU
induced
extensive
particle
aggregation.
main
NA
peak
SAXS
data
were
similar,
repeat
distance
increasing
from
polyU
Language: Английский
Citations
Bioconjugate Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown Published: Feb. 12, 2025
Brain
tumors,
particularly
glioblastomas,
represent
the
most
complicated
cancers
to
treat
and
manage
due
their
highly
invasive
nature
protective
barriers
of
brain,
including
blood-brain
barrier
(BBB).
The
efficacy
currently
available
treatments,
viz.,
radiotherapy,
chemotherapy,
immunotherapy,
are
frequently
limited
by
major
side
effects,
drug
resistance,
restricted
penetration
into
brain.
Lipid
nanoparticles
(LNPs)
have
emerged
as
a
promising
targeted
delivery
system
for
brain
tumors.
nanocarriers
gained
tremendous
attention
tumor
therapeutics
multiple
encapsulation
abilities,
controlled
release,
better
biocompatibility,
ability
cross
BBB.
Herein,
detailed
analysis
design,
mechanisms,
therapeutic
benefits
LNPs
in
treatment
is
discussed.
Moreover,
we
also
discuss
safety
issues
clinical
developments
current
future
challenges.
Further,
focused
on
transformation
therapy
eliminating
effects
engineering
overcome
related
biological
barriers,
which
provide
personalized,
affordable,
low-risk
options.
Language: Английский
Citations
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(35) Published: July 1, 2023
Ionisable
amino-lipid
is
a
key
component
in
lipid
nanoparticles
(LNPs),
which
plays
crucial
role
the
encapsulation
of
RNA
molecules,
allowing
efficient
cellular
uptake
and
then
releasing
from
acidic
endosomes.
Herein,
we
present
direct
evidence
for
remarkable
structural
transitions,
with
decreasing
membrane
curvature,
including
inverse
micellar,
to
hexagonal,
two
distinct
bicontinuous
cubic,
finally
lamellar
phase
mainstream
COVID-19
vaccine
ionisable
ALC-0315
SM-102
lipids,
occurring
upon
gradual
acidification
as
encountered
The
millisecond
kinetic
growth
cubic
hexagonal
structures
evolution
ordered
formation
lipid-RNA/DNA
complexation
are
quantitatively
revealed
by
situ
synchrotron
radiation
time-resolved
small
angle
X-ray
scattering
coupled
rapid
flow
mixing.
We
found
that
final
self-assembled
identity,
kinetics,
were
controlled
molecular
structure,
bulk
environment,
compositions,
nucleic
acid
structure/size.
implicated
link
between
curvature
LNP
endosomal
escape
helps
future
optimisation
lipids
engineering
gene
delivery.
Language: Английский
Citations
Advanced Drug Delivery Reviews,
Journal Year:
2024,
Volume and Issue:
213, P. 115419 - 115419
Published: Aug. 5, 2024
RNA
medicines
represent
a
paradigm
shift
in
treatment
and
prevention
of
critical
diseases
global
significance,
e.g.,
infectious
diseases.
The
highly
successful
messenger
(mRNA)
vaccines
against
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
were
developed
at
record
speed
during
the
disease
2019
pandemic.
A
consequence
this
is
exceptionally
shortened
vaccine
development
times,
which
combination
with
adaptability
makes
technology
attractive
for
pandemic
preparedness.
Here,
we
review
state
art
design
delivery
based
on
different
modalities,
including
linear
mRNA,
self-amplifying
RNA,
trans-amplifying
circular
RNA.
We
provide
an
overview
clinical
pipeline
diseases,
present
analytical
procedures,
are
paramount
characterizing
quality
attributes
guaranteeing
their
quality,
discuss
future
perspectives
using
to
combat
pathogens
beyond
SARS-CoV-2.
Language: Английский
Citations
Microorganisms,
Journal Year:
2024,
Volume and Issue:
12(3), P. 599 - 599
Published: March 17, 2024
Chronic
hepatitis
B
(CHB)
is
a
global
health
challenge
that
can
result
in
significant
liver-related
morbidity
and
mortality.
Despite
prophylactic
vaccine
being
available,
patients
already
living
with
CHB
often
must
engage
lifelong
therapy
nucleoside
analogues.
However,
the
potential
of
RNA
interference
(RNAi)
therapeutics
as
promising
avenue
for
treatment
explored.
RNAi,
particularly
using
small
interfering
(siRNA),
targets
viral
be
used
to
inhibit
virus
(HBV)
replication.
Several
candidates
are
currently
studied
have
exhibited
varying
success
reducing
surface
antigen
(HBsAg)
levels,
some
showing
sustained
HBsAg
loss
after
cessation
therapy.
The
dynamic
evolution
RNAi
presents
trajectory
development
effective
treatments
CHB.
This
review
highlights
recent
findings
on
therapeutics,
including
modifications
stability,
various
delivery
vectors,
specific
development.
Language: Английский
Citations
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(27) Published: April 23, 2024
Controlling
the
end-groups
of
biocompatible
polymers
is
crucial
for
enabling
polymer-based
therapeutics
and
nanomedicine.
Typically,
end-group
diversification
a
challenging
time-consuming
endeavor,
especially
prepared
via
ionic
polymerization
mechanisms
with
limited
functional
group
tolerance.
In
this
study,
we
present
facile
approach
poly(2-oxazoline)s
(POx),
quick
reliable
production
heterotelechelic
to
facilitate
POxylation.
The
relies
on
careful
tuning
reaction
parameters
establish
differential
reactivity
pentafluorobenzyl
initiator
fragment
living
oxazolinium
chain-end,
allowing
selective
introduction
N-,
S-,
O-nucleophiles
termination
polymerization,
consecutive
nucleophilic
para-fluoro
substitution.
value
accelerated
development
nanomedicine
demonstrated
through
synthesis
well-defined
lipid-polymer
conjugates
POx-polypeptide
block-copolymers,
which
are
well-suited
drug
gene
delivery.
Furthermore,
investigated
application
lipid-POx
conjugate
formulation
delivery
mRNA-loaded
lipid
nanoparticles
immunization
against
SARS-COV-2
virus,
underscoring
POx
as
polymer
platform.
Language: Английский
Citations
European Journal of Pharmaceutics and Biopharmaceutics,
Journal Year:
2025,
Volume and Issue:
209, P. 114674 - 114674
Published: Feb. 21, 2025
Language: Английский
Citations
Pharmaceutics,
Journal Year:
2024,
Volume and Issue:
16(12), P. 1521 - 1521
Published: Nov. 26, 2024
Lipid
nanoparticles
(LNPs)
have
shown
promise
as
a
delivery
system
for
nucleic
acid-based
therapeutics,
including
DNA,
siRNA,
and
mRNA
vaccines.
The
immune
plays
critical
role
in
the
response
to
these
nanocarriers,
with
innate
cells
initiating
an
early
adaptive
mediating
more
specific
reaction,
sometimes
leading
potential
adverse
effects.
Recent
studies
that
LNPs
is
mediated
by
Toll-like
receptors
(TLRs)
other
pattern
recognition
(PRRs),
which
recognize
lipid
components
of
nanoparticles.
This
can
trigger
activation
inflammatory
pathways
production
cytokines
chemokines,
effects
such
fever,
inflammation,
pain
at
injection
site.
On
hand,
appears
be
primarily
directed
against
protein
encoded
cargo,
little
evidence
ongoing
LNP
itself.
Understanding
relationship
between
development
safe
effective
systems.
In
fact,
targeting
essential
develop
vaccines,
well
therapies
cancer
or
infections.
There
lack
research
literature
has
systematically
studied
factors
influence
interaction
further
needed
better
elucidate
mechanisms
underlying
LNPs.
this
review,
we
discuss
LNPs’
composition,
physico-chemical
properties,
size,
shape,
surface
charge,
corona
formation
affect
reactivity
system,
thus
providing
guide
on
new
formulations
could
gain
favorable
efficacy/safety
profile.
Language: Английский
Citations
Lipid Nanocarriers as Precision Delivery Systems for Brain Tumors
Real‐Time pH‐Dependent Self‐Assembly of Ionisable Lipids from COVID‐19 Vaccines and In Situ Nucleic Acid Complexation
Advances in the design and delivery of RNA vaccines for infectious diseases
RNA Interference Therapeutics for Chronic Hepatitis B: Progress, Challenges, and Future Prospects
Facile Generation of Heterotelechelic Poly(2‐Oxazoline)s Towards Accelerated Exploration of Poly(2‐Oxazoline)‐Based Nanomedicine
Dual targeted lipid nanoparticles for enhanced DNA delivery and transfection of breast cancer cells
Effect of Lipid Nanoparticle Physico-Chemical Properties and Composition on Their Interaction with the Immune System