Biophysics Reports,
Journal Year:
2023,
Volume and Issue:
9(5), P. 255 - 255
Published: Jan. 1, 2023
Harnessing
surface
engineering
strategies
to
functionalize
nucleic
acid-lipid
nanoparticles
(LNPs)
for
improved
performance
has
been
a
hot
research
topic
since
the
approval
of
first
siRNA
drug,
patisiran,
and
two
mRNA-based
COVID-19
vaccines,
BNT162b2
mRNA-1273.
Currently,
efforts
have
mainly
made
construct
targeted
LNPs
organ-
or
cell-type-specific
delivery
acid
drugs
by
conjugation
with
various
types
ligands.
In
this
review,
we
describe
acid-LNPs,
considering
ligand
types,
chemistries,
incorporation
methods.
We
then
outline
general
purification
characterization
techniques
that
are
frequently
used
following
step
emphasize
specific
certain
Next,
comprehensively
summarize
currently
accessible
organs
cell
as
well
other
applications
engineered
LNPs.
Finally,
provide
considerations
formulating
discuss
challenges
successfully
translating
"proof
concept"
from
laboratory
into
clinic.
believe
addressing
these
could
accelerate
development
surface-engineered
beyond.
Pharmaceutical Research,
Journal Year:
2024,
Volume and Issue:
41(3), P. 501 - 512
Published: Feb. 7, 2024
This
study
aimed
to
test
the
feasibility
of
using
Small
Angle
X-ray
Scattering
(SAXS)
coupled
with
Density
from
Solution
(DENSS)
algorithm
characterize
internal
architecture
messenger
RNA-containing
lipid
nanoparticles
(mRNA-LNPs).
The
DENSS
was
employed
construct
a
three-dimensional
model
average
individual
mRNA-LNP.
reconstructed
models
were
cross
validated
cryogenic
transmission
electron
microscopy
(cryo-TEM),
and
dynamic
light
scattering
(DLS)
assess
size,
morphology,
structure.
Cryo-TEM
DLS
complemented
SAXS,
revealed
core–shell
mRNA-LNP
structure
electron-rich
mRNA-rich
region
at
core,
surrounded
by
lipids.
model,
utilizing
algorithm,
effectively
distinguishes
mRNA
lipids
via
density
mapping.
Notably,
accurately
morphology
mRNA-LNPs
as
an
ellipsoidal
shape
"bleb"
or
two-compartment
contrasting
densities,
corresponding
mRNA-filled
empty
compartments,
respectively.
Finally,
subtle
changes
in
LNP
after
three
freeze–thaw
cycles
detected
demonstrating
increase
radius
gyration
(Rg)
associated
leakage.
Analyzing
SAXS
profiles
based
on
yield
can
be
useful
physicochemical
characterization
method
toolbox
facilitate
their
development.
Analytical Chemistry,
Journal Year:
2024,
Volume and Issue:
96(6), P. 2464 - 2473
Published: Feb. 2, 2024
Lipid
nanoparticles
(LNPs)
are
intricate
multicomponent
systems
widely
recognized
for
their
efficient
delivery
of
oligonucleotide
cargo
to
host
cells.
Gaining
insights
into
the
molecular
properties
LNPs
is
crucial
effective
design
and
characterization.
However,
analysis
internal
structure
at
level
presents
a
significant
challenge.
This
study
introduces
31P
nuclear
magnetic
resonance
(NMR)
methods
acquire
structural
dynamic
information
about
phospholipid
envelope
LNPs.
Specifically,
we
demonstrate
that
chemical
shift
anisotropy
(CSA)
parameters
serve
as
sensitive
indicator
assembly
distearoylphosphatidylcholine
(DSPC)
lipids
within
particles.
An
analytical
protocol
measuring
CSA
developed,
which
can
be
implemented
using
either
solution
NMR
or
solid-state
NMR,
offering
wide
accessibility
adaptability.
The
capability
this
method
demonstrated
both
model
DSPC
liposomes
real-world
pharmaceutical
LNP
formulations.
Furthermore,
our
employed
investigate
impact
formulation
processes
composition
on
specifically
particles
or,
more
generally,
phospholipid-based
systems.
makes
it
an
indispensable
tool
evaluating
critical
such
homogeneity,
batch-to-batch
reproducibility,
stability
Frontiers in Molecular Biosciences,
Journal Year:
2024,
Volume and Issue:
10
Published: Jan. 3, 2024
In
recent
years,
small
non-coding
RNAs
(ncRNAs)
have
emerged
as
a
new
player
in
the
realm
of
cancer
therapeutics.
Their
unique
capacity
to
directly
modulate
genetic
networks
and
target
oncogenes
positions
them
valuable
complements
existing
small-molecule
drugs.
Concurrently,
advancement
ncRNA-based
therapeutics
has
rekindled
pursuit
efficacious
vivo
delivery
strategies.
this
review,
we
provide
an
overview
most
current
clinical
preclinical
studies
field
Furthermore,
shed
light
on
pivotal
challenges
hindering
successful
translation
these
promising
therapies
into
practice,
with
specific
focus
methods,
aiming
stimulate
innovative
approaches
address
foundational
aspect
treatment.
Expert Opinion on Drug Delivery,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 1, 2025
Introduction
Non-small
cell
lung
cancer
(NSCLC)
continues
to
pose
a
considerable
health
challenge
with
few
therapeutic
alternatives.
Liquid
crystalline
nanoparticles
(LCN)
are
nanostructured
drug
delivery
systems
made
of
lipid-based
amphiphilic
materials
that
self-assemble
into
phases
in
aqueous
environments.
LCN
have
become
promising
way
treat
NSCLC
owing
their
specific
properties
make
them
useful
for
targeted
and
controlled
release.
Advanced Materials,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 16, 2025
Abstract
Despite
increasing
knowledge
about
the
mechanistic
aspects
of
lipid
nanoparticles
(LNPs)
as
oligonucleotide
carriers,
structure‐function
relationship
in
LNPs
has
been
generally
overlooked.
Understanding
this
correlation
is
critical
rational
design
LNPs.
Here,
a
materials
characterization
approach
utilized,
applying
structural
information
from
small‐angle
X‐ray
scattering
experiments
to
novel
focusing
on
distinct
organizations
with
minimal
compositional
variation.
The
phase
structures
are
characterized
these
and
their
corresponding
bulk
mixtures
techniques,
LNP‐cell
interactions
vitro
respect
cytotoxicity,
hemolysis,
cargo
delivery,
cell
uptake,
lysosomal
swelling.
An
LNP
identified
that
outperforms
Onpattro
composition
using
components
molar
ratios
which
differ
gold
standard
clinical
base
structure
an
inverse
micellar
organization,
whereas
inverted
hexagonal
phases
not
functional,
suggesting
formation
may
be
needed
for
LNP‐mediated
delivery.
importance
stabilizer
choice
function
demonstrated
super‐resolution
microscopy
highlights
complexity
delivery
mechanisms,
where
swelling
majority
observed.
This
study
advanced
enable
relationships.
Molecular Pharmaceutics,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 26, 2025
Lipid
nanoparticles
(LNPs)
have
emerged
as
the
premier
drug
delivery
system
for
oligonucleotide
vaccines
and
therapeutics
in
recent
years.
Despite
their
prosperous
advancement
research
clinical
applications,
there
is
a
significant
lack
of
mechanistic
understanding
assembly
lipid
particles
at
molecular
level.
In
our
study,
we
utilized
combination
solution
solid-state
NMR,
together
with
dynamics
simulations,
to
elucidate
local
structures
interactions
chemical
components
across
multiple
motional
regimes.
Our
results
comprehensively
evaluated
impact
formulation
engineering
process
factors
on
particle
formation
identified
interplay
phospholipids
(DSPC),
poly(ethylene
glycol)
(PEG)
conjugates,
cholesterol
governing
size
from
structural
perspective,
using
static
31P
NMR
techniques.
These
studies
provide
novel
insights
into
properties
LNP
envelope
membrane.
Additionally,
compositional
distribution
play
critical
role
consequent
stability
potency.
this
intermolecular
contacts
among
one-dimensional
1H-13C
cross-polarization
magic
angle
spinning
experiments,
1H
relaxation
measurements,
two-dimensional
1H-1H
correlation
methods,
providing
basis
assembly.
Interestingly,
cationic
ionizable
lipids,
conventionally
regarded
stabilizing
agents
primarily
located
within
core
LNPs,
were
found
interact
PEG
lipids
coexist
outer
layer
particles.
We
suggest
that
LNPs
examined
here
are
comprised
an
rich
surrounding
region.
high-resolution
findings
offer
insightful
dynamic
details
pertaining
individual
influence
complex
structure
engineering.
