Advanced Healthcare Materials,
Journal Year:
2024,
Volume and Issue:
13(16)
Published: March 28, 2024
Abstract
Targeted
drug
delivery
and
the
reduction
of
off‐target
effects
are
crucial
for
promising
clinical
application
nucleic
acid
drugs.
To
address
this
challenge,
a
new
approach
treating
osteoarthritis
(OA)
that
accurately
delivers
antisense
oligonucleotides
(ASO)
targeting
matrix
metalloproteinase‐13
(ASO‐MMP13)
to
chondrocytes,
is
developed.
Small
extracellular
vesicles
(exos)
ligated
with
chondrocyte
affinity
peptide
(CAP)
using
Sortase
A
subsequently
incubated
cholesterol‐modified
ASO‐MMP13
construct
chondrocyte‐targeted
exo
(CAP‐exoASO).
Compared
exos
without
CAP
(ExoASO),
CAP‐exoASOs
attenuate
IL‐1β‐induced
damage
prolong
retention
time
in
joint
distribution
major
organs
following
intra‐articular
injection.
Notably,
decrease
MMP13
expression
(
P
<
0.001)
upregulate
COL2A1
=
0.006),
resulting
reorganization
cartilage
alleviation
progression
OA
model.
Furthermore,
Osteoarthritis
Research
Society
International
(OARSI)
score
articular
tissues
treated
CAP‐exoASO
comparable
healthy
rats
0.148).
mechanistic
study
demonstrates
may
reduce
inflammation
by
suppressing
IL‐17
TNF
signaling
pathways.
Based
on
targeted
effect,
successfully
accomplish
repair
have
considerable
potential
development
as
therapeutic
modality
satisfactory
therapy.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(2), P. 1417 - 1417
Published: Jan. 11, 2023
Hepatocellular
carcinoma
(HCC)
is
one
of
the
leading
causes
cancer
death
globally.
The
stem
cells
(CSCs)
HCC
are
responsible
for
tumor
growth,
invasion,
metastasis,
recurrence,
chemoresistance,
target
therapy
resistance
and
radioresistance.
reported
main
surface
markers
used
to
identify
liver
CSCs
include
epithelial
cell
adhesion/activating
molecule
(EpCAM),
cluster
differentiation
90
(CD90),
CD44
CD133.
molecular
signaling
pathways
Wnt/β-catenin,
transforming
growth
factors-β
(TGF-β),
sonic
hedgehog
(SHH),
PI3K/Akt/mTOR
Notch.
Patients
with
EpCAM-positive
alpha-fetoprotein
(AFP)-positive
usually
young
but
have
advanced
tumor-node-metastasis
(TNM)
stages.
CD90-positive
HCCs
poorly
differentiated
worse
prognosis.
Those
CD44-positive
develop
early
metastases.
CD133
expression
a
higher
recurrence
rate
shorter
overall
survival.
Wnt/β-catenin
pathway
triggers
angiogenesis,
infiltration
metastasis
through
enhancement
angiogenic
factors.
All
CD133+
CSCs,
CD133+/EpCAM+
CD44+
contribute
sorafenib
resistance.
SHH
could
protect
against
ionizing
radiation
in
an
autocrine
manner.
Reducing
CSC
population
crucial
improvement
HCC.
However,
targeting
still
challenging.
Journal of Experimental & Clinical Cancer Research,
Journal Year:
2023,
Volume and Issue:
42(1)
Published: May 23, 2023
Abstract
Cancer
stem
cells
(CSCs)
are
the
key
“seeds”
for
tumor
initiation
and
development,
metastasis,
recurrence.
Because
of
function
CSCs
in
development
progression,
research
this
field
has
intensified
viewed
as
a
new
therapeutic
target.
Exosomes
carrying
wide
range
DNA,
RNA,
lipids,
metabolites,
cytosolic
cell-surface
proteins
released
outside
originating
through
fusion
multivesicular
endosomes
or
bodies
with
plasma
membrane.
It
become
evident
that
CSC‐derived
exosomes
play
significant
role
almost
all
“hallmarks”
cancer.
For
example,
from
can
maintain
steady
state
self-renewal
microenvironment
regulate
microenvironmental
distant
to
help
cancer
escape
immune
surveillance
induce
tolerance.
However,
value
underlying
molecular
mechanisms
still
largely
undefined.
To
provide
an
overview
possible
targeting
strategies,
we
summarize
relevant
progress,
highlight
potential
impact
detecting
on
treatment,
discuss
opportunities
challenges
based
our
experience
insights
area.
A
more
thorough
understanding
characteristics
may
open
avenues
clinical
diagnostic/prognostic
tools
therapies
prevent
resistance
relapse.
Advanced Healthcare Materials,
Journal Year:
2024,
Volume and Issue:
13(16)
Published: March 28, 2024
Abstract
Targeted
drug
delivery
and
the
reduction
of
off‐target
effects
are
crucial
for
promising
clinical
application
nucleic
acid
drugs.
To
address
this
challenge,
a
new
approach
treating
osteoarthritis
(OA)
that
accurately
delivers
antisense
oligonucleotides
(ASO)
targeting
matrix
metalloproteinase‐13
(ASO‐MMP13)
to
chondrocytes,
is
developed.
Small
extracellular
vesicles
(exos)
ligated
with
chondrocyte
affinity
peptide
(CAP)
using
Sortase
A
subsequently
incubated
cholesterol‐modified
ASO‐MMP13
construct
chondrocyte‐targeted
exo
(CAP‐exoASO).
Compared
exos
without
CAP
(ExoASO),
CAP‐exoASOs
attenuate
IL‐1β‐induced
damage
prolong
retention
time
in
joint
distribution
major
organs
following
intra‐articular
injection.
Notably,
decrease
MMP13
expression
(
P
<
0.001)
upregulate
COL2A1
=
0.006),
resulting
reorganization
cartilage
alleviation
progression
OA
model.
Furthermore,
Osteoarthritis
Research
Society
International
(OARSI)
score
articular
tissues
treated
CAP‐exoASO
comparable
healthy
rats
0.148).
mechanistic
study
demonstrates
may
reduce
inflammation
by
suppressing
IL‐17
TNF
signaling
pathways.
Based
on
targeted
effect,
successfully
accomplish
repair
have
considerable
potential
development
as
therapeutic
modality
satisfactory
therapy.
