ACS Nano,
Год журнала:
2024,
Номер
18(27), С. 17749 - 17763
Опубликована: Июнь 27, 2024
The
rapid
development
of
the
SARS-CoV-2
vaccine
has
been
used
to
prevent
spread
coronavirus
2019
(COVID-19).
However,
ongoing
and
future
pandemics
caused
by
variants
mutations
underscore
need
for
effective
vaccines
that
provide
broad-spectrum
protection.
Here,
we
developed
a
nanoparticle
with
broad
protection
against
divergent
variants.
corresponding
conserved
epitopes
preexisting
neutralizing
(CePn)
antibody
were
presented
on
self-assembling
Helicobacter
pylori
ferritin
generate
CePnF
nanoparticle.
Intranasal
immunization
mice
nanoparticles
induced
robust
humoral,
cellular,
mucosal
immune
responses
long-lasting
immunity.
CePnF-induced
antibodies
exhibited
cross-reactivity
activity
different
coronaviruses
(CoVs).
vaccination
significantly
inhibited
replication
pathology
Delta,
WIV04,
Omicron
strains
in
hACE2
transgenic
and,
thus,
conferred
these
Our
constructed
nanovaccine
targeting
can
serve
as
promising
candidate
universal
vaccine.
Advanced Materials,
Год журнала:
2024,
Номер
36(29)
Опубликована: Апрель 24, 2024
Abstract
The
advancement
of
message
RNA
(mRNA)
‐based
immunotherapies
for
cancer
is
highly
dependent
on
the
effective
delivery
(Ribonucleic)
payloads
using
ionizable
lipid
nanoparticles
(LNPs).
However,
clinical
application
these
therapies
hindered
by
variable
mRNA
expression
among
different
types
and
risk
systemic
toxicity.
transient
profile
further
complicates
this
issue,
necessitating
frequent
dosing
thus
increasing
potential
adverse
effects.
Addressing
challenges,
a
high‐throughput
combinatorial
method
utilized
to
synthesize
screen
LNPs
that
efficiently
deliver
circular
(circRNA)
lung
tumors.
lead
LNP,
H1L1A1B3,
demonstrates
fourfold
increase
in
circRNA
transfection
efficiency
cells
over
ALC‐0315,
industry‐standard
LNPs,
while
providing
potent
immune
activation.
A
single
intratumoral
injection
H1L1A1B3
loaded
with
encoding
interleukin‐12
(IL‐12),
induces
robust
response
Lewis
carcinoma
model,
leading
marked
tumor
regression.
Immunological
profiling
treated
tumors
reveals
substantial
increments
CD45
+
leukocytes
enhances
infiltration
CD8
T
cells,
underscoring
ability
modulate
microenvironment
favorably.
These
results
highlight
tailored
LNP
platforms
advance
drug
therapy,
broadening
prospects
immunotherapeutics.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июль 26, 2024
Abstract
Ionizable
lipid
nanoparticles
(LNPs)
are
seeing
widespread
use
in
mRNA
delivery,
notably
SARS-CoV-2
vaccines.
However,
the
expansion
of
therapies
beyond
COVID-19
is
impeded
by
absence
LNPs
tailored
for
diverse
cell
types.
In
this
study,
we
present
AI-Guided
Lipid
Engineering
(AGILE)
platform,
a
synergistic
combination
deep
learning
and
combinatorial
chemistry.
AGILE
streamlines
ionizable
development
with
efficient
library
design,
silico
screening
via
neural
networks,
adaptability
to
lines.
Using
AGILE,
rapidly
synthesize,
evaluate
lipids
selecting
from
vast
library.
Intriguingly,
reveals
cell-specific
preferences
lipids,
indicating
tailoring
optimal
delivery
varying
These
highlight
AGILE’s
potential
expediting
customized
LNPs,
addressing
complex
needs
clinical
practice,
thereby
broadening
scope
efficacy
therapies.
Advanced Drug Delivery Reviews,
Год журнала:
2024,
Номер
206, С. 115190 - 115190
Опубликована: Фев. 1, 2024
mRNA-based
vaccines
are
emerging
as
a
promising
alternative
to
standard
cancer
treatments
and
the
conventional
vaccines.
Moreover,
FDA-approval
of
three
nucleic
acid
based
therapeutics
(Onpattro,
BNT162b2
mRNA-1273)
has
further
increased
interest
trust
on
this
type
therapeutics.
In
order
achieve
significant
therapeutic
efficacy,
mRNA
needs
from
drug
delivery
system.
last
years,
several
platforms
have
been
explored,
being
lipid
nanoparticles
(LNPs)
most
well
characterized
studied.
A
better
understanding
how
operate
(both
itself
system)
will
help
improve
their
efficacy
safety.
review,
we
provide
an
overview
what
mode
action
highlight
advantages
challenges
different
that
under
investigation.
Nanoparticle-based
cancer
immunotherapy
has
shown
promising
therapeutic
potential
in
clinical
settings.
However,
current
research
mainly
uses
nanoparticles
as
delivery
vehicles
but
overlooks
their
to
directly
modulate
immune
responses.
Inspired
by
the
endogenous
endoplasmic
reticulum
(ER)
stress
caused
unfolded/misfolded
proteins,
we
present
a
rationally
designed
immunogenic
cell
death
(ICD)
inducer
named
NanoICD,
which
is
nanoparticle
engineered
for
ER
targeting
and
retention.
By
carefully
controlling
surface
composition
properties,
have
obtained
NanoICD
that
can
effectively
accumulate
ER,
induce
stress,
activate
ICD-associated
In
addition,
generally
applicable
various
proteins
enzymes
further
enhance
immunomodulatory
capacity,
exemplified
encapsulating
catalase
(CAT)
obtain
NanoICD/CAT,
alleviated
immunosuppressive
tumor
microenvironment
induced
robust
antitumor
responses
4T1-bearing
mice.
This
work
demonstrates
nanostructures'
autonomously
regulate
biological
processes
provides
insights
into
development
of
advanced
nanomedicines
treatment.
Journal of Biomedical Materials Research Part A,
Год журнала:
2024,
Номер
112(9), С. 1494 - 1505
Опубликована: Март 15, 2024
RNA-based
therapeutics
have
gained
traction
for
the
prevention
and
treatment
of
a
variety
diseases.
However,
their
fragility
immunogenicity
necessitate
drug
carrier.
Lipid
nanoparticles
(LNPs)
emerged
as
predominant
delivery
vehicle
RNA
therapeutics.
An
important
component
LNPs
is
ionizable
lipid
(IL),
which
protonated
in
acidic
environment
endosome,
prompting
cargo
release
into
cytosol.
Currently,
there
growing
evidence
that
structure
IL
tails
significantly
impacts
efficacy
LNP-mediated
mRNA
translation.
Here,
we
optimized
tail
length
three
different
cargos.
Using
C12-200,
gold
standard
IL,
model,
designed
library
ILs
with
varying
lengths
evaluated
potency
vivo.
We
demonstrated
small
changes
lipophilicity
can
drastically
increase
or
decrease
identified
formulated
firefly
luciferase
(1929
base
pairs)
C10-200,
an
shorter
than
enhance
liver
transfection
by
over
10-fold.
Furthermore,
were
found
to
be
ideal
encapsulating
cargos
sizes.
erythropoietin
(EPO),
responsible
stimulating
red
blood
cell
production,
(858
pairs),
C13-200
led
EPO
translation
at
levels
similar
C12-200
LNP.
The
Cas9
(4521
C9-200
induced
times
quantity
indels
compared
Our
findings
suggest
may
lead
higher
larger
mRNAs,
longer
more
efficacious
delivering
smaller
envision
results
this
project
utilized
future
design
criteria
next
generation
LNP
systems
Nucleic
acid
therapeutics
represent
a
highly
promising
treatment
approach
in
modern
medicine,
treating
diseases
at
the
genetic
level.
However,
these
face
numerous
challenges
practical
applications,
particularly
regarding
their
stability,
effectiveness,
cellular
uptake
efficiency,
and
limitations
delivering
them
specifically
to
target
tissues.
To
overcome
obstacles,
researchers
have
developed
various
innovative
delivery
systems,
including
viral
vectors,
lipid
nanoparticles,
polymer
inorganic
protein
carriers,
exosomes,
antibody
oligonucleotide
conjugates,
DNA
nanostructure-based
systems.
These
systems
enhance
therapeutic
efficacy
of
nucleic
drugs
by
improving
targeting
specificity,
half-life
vivo.
In
this
review,
we
systematically
discuss
different
types
drugs,
analyze
major
barriers
encountered
delivery,
summarize
current
research
progress
emerging
We
also
highlight
latest
advancements
application
for
diseases,
infectious
cancer,
brain
wound
healing.
This
review
aims
provide
comprehensive
overview
drug
systems'
status
future
directions
integrating
nanotechnology,
biomaterials
science,
gene
editing
technologies,
emphasizing
transformative
potential
precision
medicine.
