Langmuir,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 13, 2025
Ribonucleic
acid
(RNA)
nanocarriers,
specifically
lipid
nanoparticles
and
polymeric
nanoparticles,
enable
RNA
transfection
both
in
vitro
vivo;
however,
only
a
small
percentage
of
endocytosed
by
cell
is
delivered
to
the
cytosolic
machinery,
minimizing
its
effect.
nanocarriers
face
two
major
obstacles
after
endocytosis:
endosomal
escape
release.
Overcoming
simultaneously
challenging
because
usually
achieved
using
high
positive
charge
disrupt
membrane.
However,
this
typically
also
inhibits
release
anionic
strongly
bound
nanocarrier
electrostatic
interactions.
Many
address
one
over
other
despite
growing
body
evidence
demonstrating
that
are
crucial
for
transfection.
In
review,
we
survey
various
strategies
have
been
employed
accomplish
with
focus
on
nanomaterials.
We
first
consider
requirements
must
achieve
delivery
including
protection
from
degradation,
cellular
internalization,
escape,
then
discuss
current
polymers
used
examine
achieving
Finally,
review
stimuli-responsive
While
continues
be
challenge
efficient
transfection,
many
new
innovations
materials
elucidated
promising
strategies.
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 1, 2025
Lipid
nanoparticles
(LNPs)
have
emerged
as
pivotal
vehicles
for
messenger
RNA
(mRNA)
delivery
to
hepatocytes
upon
systemic
administration
and
antigen-presenting
cells
following
intramuscular
injection.
However,
achieving
mRNA
non-hepatocytes
remains
challenging
without
the
incorporation
of
targeting
ligands
such
antibodies,
peptides,
or
small
molecules.
Inspired
by
comb-like
polymeric
architecture,
here
we
utilized
a
multiarm-assisted
design
construct
library
270
dendron-like
degradable
ionizable
lipids
altering
structures
amine
heads
multiarmed
tails
optimal
delivery.
Following
in
vitro
high-throughput
screening,
series
top-dendron-like
LNPs
with
high
transfection
efficacy
were
identified.
These
facilitated
greater
spleen
vivo
compared
lipid
analogs
lacking
structure.
Proteomic
analysis
corona-LNP
pellets
showed
enhancement
key
protein
clusters,
suggesting
potential
endogenous
spleen.
A
lead
LNP
formulation,
18-2-9b2,
was
further
used
encapsulate
Cre
demonstrated
excellent
genome
modification
splenic
macrophages,
outperforming
spleen-tropic
MC3/18PA
Ai14
mice
model.
Moreover,
18-2-9b2
encapsulating
therapeutic
BTB
domain
CNC
homologue
1
(BACH1)
exhibited
proficient
BACH1
expression
subsequent
Spic
downregulation
red
pulp
macrophages
(RPM)
Spic-GFP
transgene
model
intravenous
administration.
results
underscore
facilitatem
potentially
opening
avenues
range
mRNA-LNP
applications,
including
regenerative
medicine,
replacement,
gene
editing
therapies.
ACS Nano,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 17, 2025
Since
their
inception
in
the
early
1960s,
development
and
use
of
nanoscale
materials
have
progressed
tremendously,
roles
diverse
fields
ranging
from
human
health
to
energy
electronics
are
undeniable.
The
application
nanotechnology
inventions
has
revolutionized
many
aspects
everyday
life
including
various
medical
applications
specifically
drug
delivery
systems,
maximizing
therapeutic
efficacy
contained
drugs
by
means
bioavailability
enhancement
or
minimization
adverse
effects.
In
this
review,
we
utilize
CAS
Content
Collection,
a
vast
repository
scientific
information
extracted
journal
patent
publications,
analyze
trends
nanoscience
research
relevant
an
effort
provide
comprehensive
detailed
picture
field.
We
examine
publication
landscape
area
insights
into
current
knowledge
advances
developments.
review
major
classes
nanosized
routes,
targeted
diseases.
outline
most
discussed
concepts
assess
advantages
nanocarriers.
objective
is
broad
overview
evolving
regarding
challenges,
evaluate
growth
opportunities.
merit
stems
extensive,
wide-ranging
coverage
up-to-date
information,
allowing
unmatched
breadth
analysis
in-depth
insights.
ACS Nano,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 17, 2025
Messenger
RNA
(mRNA)
encoding
base
editors,
along
with
single
guide
RNAs
(sgRNAs),
have
emerged
as
a
promising
therapeutic
approach
for
various
disorders.
However,
there
is
still
insufficient
exploration
in
achieving
targeted
and
efficient
delivery
of
mRNA
sgRNA
to
multiple
organs
while
ensuring
high
biocompatibility
stability
vivo.
To
address
this
challenge,
we
synthesized
library
108
poly(β-amino)
esters
(PBAEs)
by
incorporating
100%
hydrophobic
side
chains
end-caps
varying
amines.
These
PBAEs
were
further
formulated
other
excipients,
including
helper
lipids,
cholesterol,
PEGylated
form
polymer–lipid
nanoparticles
(PLNPs).
Structure–function
analysis
revealed
that
eLog
P
could
serve
predictive
parameter
determining
the
liver
or
lung
tropism
PLNPs.
The
end-capped
monoamines
was
significantly
higher
compared
those
diamines.
Leveraging
these
findings,
expanded
PBAE
identified
leading
(7C8C8)
efficiency
outperforming
current
FDA-approved
ionizable
lipids
(ALC-0315,
SM-102,
Dlin-MC3-DMA).
LD50
empty
PLNPs
determined
be
403.8
±
49.46
mg/kg,
indicating
safety
profile.
Additionally,
demonstrated
sustained
transfection
activity
at
least
2
months
when
stored
−20
°C
after
freezing
4
following
lyophilization.
Subsequently,
vivo
editing
using
achieved
an
impressive
approximately
70%
significant
reduction
protein
levels
exceeding
90%.
Notably,
synergistic
effects
observed
through
simultaneous
disruption
proprotein
convertase
subtilisin/kexin
type
9
angiopoietin-like
3
genes,
resulting
low-density
lipoprotein
cholesterol
over
60%
several
months.
compelling
findings
provide
strong
support
development
platforms
mRNA-based
therapies.
Journal of Controlled Release,
Journal Year:
2024,
Volume and Issue:
375, P. 366 - 388
Published: Sept. 18, 2024
Recent
advancements
in
RNA
therapeutics
highlight
the
critical
need
for
precision
gene
delivery
systems
that
target
specific
organs
and
cells.
Lipid
nanoparticles
(LNPs)
have
emerged
as
key
vectors
delivering
mRNA
siRNA,
offering
protection
against
enzymatic
degradation,
enabling
targeted
cellular
uptake,
facilitating
cargo
release
into
cytosol.
This
review
discusses
development
optimization
of
organ-
cell-specific
LNPs,
focusing
on
their
design,
mechanisms
action,
therapeutic
applications.
We
explore
innovations
such
DNA/RNA
barcoding,
which
facilitates
high-throughput
screening
precise
adjustments
formulations.
address
major
challenges,
including
improving
endosomal
escape,
minimizing
off-target
effects,
enhancing
efficiencies.
Notable
clinical
trials
recent
FDA
approvals
illustrate
practical
applications
future
potential
LNP-based
therapies.
Our
findings
suggest
while
considerable
progress
has
been
made,
continued
research
is
essential
to
resolve
existing
limitations
bridge
gap
between
pre-clinical
evaluation
safety
efficacy
therapeutics.
highlights
dynamic
LNP
research.
It
outlines
a
roadmap
RNA-based
medicine.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(18), P. 10166 - 10166
Published: Sept. 22, 2024
Lipid
nanoparticles
(LNPs)
have
emerged
as
leading
non-viral
carriers
for
messenger
RNA
(mRNA)
delivery
in
clinical
applications.
Overcoming
challenges
safe
and
effective
mRNA
to
target
tissues
cells,
along
with
controlling
release
from
the
vehicle,
remains
pivotal
mRNA-based
therapies.
This
review
elucidates
structure
of
LNPs,
mechanism
delivery,
targeted
LNPs
various
cells
tissues,
including
leukocytes,
T-cells,
dendritic
Kupffer
hepatic
endothelial
extrahepatic
tissues.
Here,
we
discuss
applications
mRNA-LNP
vaccines
prevention
infectious
diseases
treatment
cancer
genetic
diseases.
Although
remain
terms
efficiency,
specific
tissue
targeting,
toxicity,
storage
stability,
technology
holds
extensive
potential
Messenger
RNA
(mRNA)
has
emerged
as
an
innovative
therapeutic
modality,
offering
promising
avenues
for
the
prevention
and
treatment
of
a
variety
diseases.
The
tremendous
success
mRNA
vaccines
in
effectively
combatting
coronavirus
disease
2019
(COVID-19)
evidences
unlimited
medical
potential
technology.
Overcoming
challenges
related
to
stability,
immunogenicity,
precision
targeting
been
made
possible
by
recent
advancements
lipid
nanoparticles
(LNPs).
This
review
summarizes
state-of-the-art
LNP-mRNA-based
therapeutics,
including
their
structure,
material
compositions,
design
guidelines,
screening
principles.
Additionally,
we
highlight
current
preclinical
clinical
trends
LNP-mRNA
therapeutics
broad
range
treatments
ophthalmological
conditions,
cancer
immunotherapy,
gene
editing,
rare-disease
medicine.
Particular
attention
is
given
translation
evolution
into
broader
spectrum
therapeutics.
We
explore
concerns
aspects
inadequate
extrahepatic
efficacy,
elevated
doses,
safety
concerns,
large-scale
production
procedures.
discussion
may
offer
insights
perspectives
on
near-
long-term
development
prospects
