Periodontitis
is
an
intractable
chronic
inflammatory
disease
characterized
by
excessive
proinflammatory
factors
production
and
reactive
oxygen
species
(ROS)
accumulation.
Nanodrugs
have
made
significant
contributions
in
the
biomedical
field
but
fall
short
as
periodontitis
therapeutics
because
of
their
singular
effects,
low
retention
rates,
poor
specificity,
insufficient
biocompatibility.
Herein,
we
report
a
functionalized
periodontal
ligament
stem
cell
(PDLSC)
membrane-camouflaged
MnO2
nanoplatform
(MnO2@hPM)
to
target
reprogram
microenvironment
periodontitis.
PDLSC-affinity
biological
molecules
hypoxia-educated
proteins
on
membrane
coating
endow
MnO2@hPM
with
capacities
actively
PDLSCs
under
environment,
concurrently
neutralize
various
factors,
scavenge
overburdened
ROS.
The
synergistic
effects
inflammation
inhibition
ROS
elimination
mitigate
mitochondrial
dysfunction,
improve
metabolic
disturbance,
restore
osteogenic
potential
inflammation-impaired
PDLSCs.
In
vivo,
effectively
accumulates
at
sites,
significantly
ameliorates
inflammation,
alleviates
bone
loss
artificial
periodontitis,
showing
optimized
therapeutic
performance
for
tissue
reconstruction.
This
multirisk-rescuing
biomimetic
nanozyme
good
biocompatibility
exhibits
inflammation-targeting
ability
benefits
against
highlighting
its
advanced
therapy
other
diseases.
ACS Nano,
Год журнала:
2024,
Номер
18(11), С. 8392 - 8410
Опубликована: Март 7, 2024
Therapeutic
antibodies
that
block
vascular
endothelial
growth
factor
(VEGF)
show
clinical
benefits
in
treating
nonsmall
cell
lung
cancers
(NSCLCs)
by
inhibiting
tumor
angiogenesis.
Nonetheless,
the
therapeutic
effects
of
systemically
administered
anti-VEGF
are
often
hindered
NSCLCs
because
their
limited
distribution
lungs
and
adverse
on
normal
tissues.
These
challenges
can
be
overcome
delivering
mRNA
form
to
cells,
a
primary
target
VEGF-mediated
pulmonary
angiogenesis,
suppress
NSCLCs.
In
this
study,
we
synthesized
derivatives
poly(β-amino
esters)
(PBAEs)
prepared
nanoparticles
encapsulate
synthetic
encoding
bevacizumab,
an
antibody
used
clinic.
Optimization
nanoparticle
formulations
resulted
selective
transfection
after
intravenous
administration.
Notably,
optimized
PBAE
were
distributed
resulting
secretion
bevacizumab.
We
analyzed
protein
corona
lung-
spleen-targeting
using
proteomics
found
distinctive
features
potentially
contributing
organ-selectivity.
Lastly,
bevacizumab
delivered
lung-targeting
more
significantly
inhibited
proliferation
angiogenesis
than
recombinant
orthotopic
NSCLC
mouse
models,
supporting
potential
therapy
its
delivery
through
nanoparticles.
Our
proof-of-principle
results
highlight
nanoparticle-mediated
anticancer
treatment
preclinical
models.
Journal of Controlled Release,
Год журнала:
2024,
Номер
375, С. 366 - 388
Опубликована: Сен. 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.
Journal of Nanobiotechnology,
Год журнала:
2024,
Номер
22(1)
Опубликована: Июль 18, 2024
Abstract
Rheumatoid
arthritis
(RA)
is
a
chronic
autoimmune
disease
marked
by
synovitis
and
cartilage
destruction.
The
active
compound,
icariin
(ICA),
derived
from
the
herb
Epimedium,
exhibits
potent
anti-inflammatory
properties.
However,
its
clinical
utility
limited
water
insolubility,
poor
permeability,
low
bioavailability.
To
address
these
challenges,
we
developed
multifunctional
drug
delivery
system—adipose-derived
stem
cells-exosomes
(ADSCs-EXO)-ICA
to
target
macrophages
in
synovial
tissue
modulate
macrophage
polarization
M1
M2.
High-performance
liquid
chromatography
analysis
confirmed
92.4
±
0.008%
loading
efficiency
for
ADSCs-EXO-ICA.
In
vitro
studies
utilizing
cellular
immunofluorescence
(IF)
flow
cytometry
demonstrated
significant
inhibition
of
proliferation
Enzyme-linked
immunosorbent
assay,
transcriptomics,
real-time
quantitative
PCR
indicated
that
ADSCs-EXO-ICA
promotes
an
M1-to-M2
phenotypic
transition
reducing
glycolysis
through
ERK/HIF-1α/GLUT1
pathway.
vivo,
effectively
accumulated
joints.
Pharmacodynamic
assessments
revealed
decreased
cytokine
levels
mitigated
symptoms
collagen-induced
(CIA)
rats.
Histological
micro
computed
tomography
markedly
ameliorated
preserved
cartilage.
Further
vivo
suppresses
promoting
switch
suppressing
glycolysis.
Western
blotting
supported
therapeutic
efficacy
RA,
confirming
role
modulating
function
energy
metabolism
regulation.
Thus,
this
study
not
only
introduces
system
significantly
enhances
anti-RA
but
also
elucidates
mechanism
action
inhibition.
Graphical
abstract
Advanced Materials,
Год журнала:
2024,
Номер
36(33)
Опубликована: Июнь 18, 2024
Tissue-specific
delivery
of
oligonucleotide
therapeutics
beyond
the
liver
remains
a
key
challenge
in
nucleic
acid
drug
development.
To
address
this
issue,
exploiting
exosomes
as
novel
carrier
has
emerged
promising
approach
for
efficient
delivery.
However,
current
exosome-based
systems
still
face
multiple
hurdles
their
clinical
applications.
Herein,
work
presents
strategy
constructing
hybrid
exosome
vehicle
(HEV)
through
DNA
zipper-mediated
membrane
fusion
tissue-specific
siRNA
As
proof-of-concept,
successfully
fuses
liposome
encapsulating
anti-NFKBIZ
siRNAs
with
corneal
epithelium
cell
(CEC)-derived
to
form
HEV
construct
treatment
dry
eye
disease
(DED).
With
homing
characteristics
inherited
from
exosomes,
siRNA-bearing
can
target
its
parent
cells
and
efficiently
deliver
payloads
cornea.
Subsequently,
NFKBIZ
gene
silencing
significantly
reduces
pro-inflammatory
cytokine
secretions
ocular
surface,
reshapes
inflammatory
microenvironment,
ultimately
achieves
an
excellent
therapeutic
outcome
DED
mouse
model.
versatile
platform,
targeting
capability
designed
may
hold
great
potential
various
treatments.
Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(32)
Опубликована: Июль 30, 2024
Monogenic
blood
diseases
are
among
the
most
common
genetic
disorders
worldwide.
These
result
in
significant
pediatric
and
adult
morbidity,
some
can
death
prior
to
birth.
Novel
ex
vivo
hematopoietic
stem
cell
(HSC)
gene
editing
therapies
hold
tremendous
promise
alter
therapeutic
landscape
but
not
without
potential
limitations.
In
offer
a
potentially
safer
more
accessible
treatment
for
these
hindered
by
lack
of
delivery
vectors
targeting
HSCs,
which
reside
difficult-to-access
bone
marrow
niche.
Here,
we
propose
that
this
biological
barrier
be
overcome
taking
advantage
HSC
residence
easily
liver
during
fetal
development.
To
facilitate
cargo
developed
an
ionizable
lipid
nanoparticle
(LNP)
platform
CD45
receptor
on
surface
HSCs.
After
validating
targeted
LNPs
improved
messenger
ribonucleic
acid
(mRNA)
lineage
cells
via
CD45-specific
mechanism
vitro,
demonstrated
mediated
safe,
potent,
long-term
modulation
HSCs
multiple
mouse
models.
We
further
optimized
LNP
vitro
encapsulate
deliver
CRISPR-based
nucleic
cargos.
Finally,
showed
enhanced
at
proof-of-concept
locus
after
single
utero
intravenous
injection.
By
development,
our
Systematically
Targeted
Editing
Machinery
(STEM)
may
provide
translatable
strategy
treat
monogenic
before
Bioconjugate Chemistry,
Год журнала:
2024,
Номер
35(4), С. 453 - 456
Опубликована: Март 16, 2024
mRNA
therapeutics
hold
great
promise
for
disease
treatment,
yet
a
key
challenge
lies
in
achieving
site-specific
delivery
to
maximize
therapeutic
efficacy
while
minimizing
off-target
side
effects.
This
viewpoint
delves
into
multiple
complementary
targeting
strategies
achieve
precise
delivery,
covering
topics
of
administration
routes,
passive
targeting,
and
active
targeting.
It
highlights
the
critical
importance
rationally
designed
nanocarriers
obtaining
desired
effects
accelerating
clinical
translation
therapeutics.
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 8, 2025
Oligonucleotides
have
emerged
as
a
formidable
new
class
of
nucleic
acid
therapeutics.
Fully
modified
oligonucleotides
exhibit
enhanced
metabolic
stability
and
display
successful
clinical
applicability
for
targets
formerly
considered
"undruggable".
Accumulating
studies
show
that
conjugation
to
targeting
modalities
stabilized
oligonucleotides,
especially
small
interfering
RNAs
(siRNAs),
has
enabled
robust
delivery
intended
cells/tissues.
However,
the
major
challenge
in
field
been
targeted
(siRNAs
antisense
(ASOs))
extrahepatic
tissues.
In
this
Perspective,
we
review
chemistry
innovations
emerging
approaches
revolutionized
oligonucleotide
drug
discovery
development.
We
explore
findings
from
both
academia
industry
highlight
potential
indications
involving
different
organs─including
skeletal
muscles,
brain,
lungs,
skin,
heart,
adipose
tissue,
eyes.
all,
continued
advances
coupled
with
conjugation-based
or
novel
administration
routes
will
further
advance
