Molecules,
Journal Year:
2019,
Volume and Issue:
24(20), P. 3744 - 3744
Published: Oct. 17, 2019
The
cellular
transport
process
of
DNA
is
hampered
by
cell
membrane
barriers,
and
hence,
a
delivery
vehicle
essential
for
realizing
the
potential
benefits
gene
therapy
to
combat
variety
genetic
diseases.
Virus-based
vehicles
are
effective,
although
immunogenicity,
toxicity
cancer
formation
among
major
limitations
this
approach.
Cationic
polymers,
such
as
polyethyleneimine
capable
condensing
nanoparticles
facilitate
delivery.
Lack
biodegradation
polymeric
poses
significant
because
accumulation
polymers
in
tissue.
Many
attempts
have
been
made
develop
biodegradable
modifying
existing
and/or
using
natural
polymers.
This
review
summarizes
mechanistic
aspects
development
Accounts of Chemical Research,
Journal Year:
2021,
Volume and Issue:
55(1), P. 2 - 12
Published: Dec. 1, 2021
ConspectusLipid
nanoparticles
(LNPs)
are
a
type
of
lipid
vesicles
that
possess
homogeneous
core.
These
widely
used
in
small-molecule
drug
and
nucleic
acid
delivery
recently
gained
much
attention
because
their
remarkable
success
as
platform
for
COVID-19
mRNA
vaccines.
Nonetheless,
the
utility
transient
protein
expression
induced
by
extends
far
beyond
vaccines
against
infectious
diseases─they
also
hold
promise
cancer
vaccines,
replacement
therapies,
gene
editing
components
rare
genetic
diseases.
However,
naked
is
inherently
unstable
prone
to
rapid
degradation
nucleases
self-hydrolysis.
Encapsulation
within
LNPs
protects
from
extracellular
ribonucleases
assists
with
intracellular
delivery.In
this
Account,
we
discuss
core
features
RNA
delivery.
We
focus
our
on
designed
deliver
mRNA;
however,
include
examples
siRNA-LNP
where
appropriate
highlight
commonalities
dissimilarities
due
structure.
First,
introduce
concept
LNPs,
advantages
disadvantages
utilizing
acids
therapeutic
agents,
general
reasoning
behind
molecular
makeup
LNPs.
briefly
most
recent
clinical
successes
LNP-based
therapies.
Second,
describe
theory
methods
LNP
self-assembly.
The
common
idea
all
preparation
inducing
electrostatic
interactions
between
charged
lipids
promoting
nanoparticle
growth
via
hydrophobic
interactions.
Third,
break
down
composition
special
fundamental
properties
purposes
each
component.
This
includes
identified
design
criteria,
commercial
sourcing,
impact
trafficking,
contribution
One
key
ionizable
lipids,
which
initiate
binding
endosomal
membranes
facilitate
cytosolic
release;
roles
other
should
not
be
disregarded,
they
associated
stability,
clearance,
distribution
Fourth,
review
attributes
constructs
whole
can
heavily
influence
size,
charge,
internal
structure,
packing,
membrane
hydration,
affinity
toward
biomacromolecules.
specific
techniques
examine
these
how
adjusted.
Finally,
offer
perspective
future
therapies
some
questions
remain
realm
formulation
optimization.
Vaccines,
Journal Year:
2021,
Volume and Issue:
9(1), P. 65 - 65
Published: Jan. 19, 2021
The
recent
success
of
mRNA
vaccines
in
SARS-CoV-2
clinical
trials
is
part
due
to
the
development
lipid
nanoparticle
delivery
systems
that
not
only
efficiently
express
mRNA-encoded
immunogen
after
intramuscular
injection,
but
also
play
roles
as
adjuvants
and
vaccine
reactogenicity.
We
present
an
overview
then
focus
on
nanoparticles
used
current
trials.
review
concludes
with
analysis
determinants
performance
vaccines.
International Journal of Molecular Sciences,
Journal Year:
2020,
Volume and Issue:
22(1), P. 385 - 385
Published: Dec. 31, 2020
The
field
of
nanotechnology
has
grown
over
the
last
two
decades
and
made
transition
from
benchtop
to
applied
technologies.
Nanoscale-sized
particles,
or
nanoparticles,
have
emerged
as
promising
tools
with
broad
applications
in
drug
delivery,
diagnostics,
cosmetics
several
other
biological
non-biological
areas.
These
advances
lead
questions
about
nanoparticle
safety.
Despite
considerable
efforts
understand
toxicity
safety
these
many
are
not
yet
fully
answered.
Nevertheless,
identified
approaches
minimize
prevent
promote
safer
nanotechnology.
This
review
summarizes
our
current
knowledge
on
their
toxic
effects,
interactions
mammalian
cells
finally
minimizing
toxicity.
Nature Communications,
Journal Year:
2020,
Volume and Issue:
11(1)
Published: Feb. 20, 2020
Endosomal
sequestration
of
lipid-based
nanoparticles
(LNPs)
remains
a
formidable
barrier
to
delivery.
Herein,
structure-activity
analysis
cholesterol
analogues
reveals
that
incorporation
C-24
alkyl
phytosterols
into
LNPs
(eLNPs)
enhances
gene
transfection
and
the
length
tail,
flexibility
sterol
ring
polarity
due
-OH
group
is
required
maintain
high
transfection.
Cryo-TEM
displays
polyhedral
shape
for
eLNPs
compared
spherical
LNPs,
while
x-ray
scattering
shows
little
disparity
in
internal
structure.
exhibit
higher
cellular
uptake
retention,
potentially
leading
steady
release
from
endosomes
over
time.
3D
single-particle
tracking
enhanced
intracellular
diffusivity
relative
suggesting
eLNP
traffic
productive
pathways
escape.
Our
findings
show
importance
subcellular
transport
carrying
mRNA
emphasize
need
greater
insights
surface
composition
structural
properties
nanoparticles,
their
interactions
which
enable
designs
improve
endosomal
Cell Death and Disease,
Journal Year:
2022,
Volume and Issue:
13(7)
Published: July 23, 2022
Abstract
The
growing
understanding
of
RNA
functions
and
their
crucial
roles
in
diseases
promotes
the
application
various
RNAs
to
selectively
function
on
hitherto
“undruggable”
proteins,
transcripts
genes,
thus
potentially
broadening
therapeutic
targets.
Several
RNA-based
medications
have
been
approved
for
clinical
use,
while
others
are
still
under
investigation
or
preclinical
trials.
Various
techniques
explored
promote
intracellular
trafficking
metabolic
stability,
despite
significant
challenges
developing
therapeutics.
In
this
review,
mechanisms
action,
challenges,
solutions,
therapeutics
comprehensively
summarized.
