Abstract
In
situ
precise
detection
of
bioactive
molecules
with
high
sensitivity
and
spatiotemporal
resolution
is
essential
for
studying
physiological
events
disease
diagnosis.
The
utilization
versatile
fluorescent
probes
in
fluorescence
imaging
offers
a
powerful
tool
vivo
biomarkers
closely
associated
pathological
conditions.
However,
the
dynamic
behavior
leading
to
rapid
clearance
small
molecule
from
regions
interest
severely
compromises
their
potential
imaging.
Notably,
self‐immobilizing
that
selectively
recognize
diseased
tissues
while
improving
retention
enrichment
enable
accurate
high‐fidelity
this
review,
we
aim
summarize
strategies
employed
recent
advances
performance
precision
using
techniques.
Lastly,
discuss
prospects
challenges
promote
further
development
application
more
delicate
probes.
Journal of Hematology & Oncology,
Год журнала:
2023,
Номер
16(1)
Опубликована: Июль 31, 2023
Abstract
NEDDylation,
a
post-translational
modification
through
three-step
enzymatic
cascades,
plays
crucial
roles
in
the
regulation
of
diverse
biological
processes.
NEDD8-activating
enzyme
(NAE)
as
only
activation
NEDDylation
has
become
an
attractive
target
to
develop
anticancer
drugs.
To
date,
numerous
inhibitors
or
agonists
targeting
NAE
have
been
developed.
Among
them,
covalent
such
MLN4924
and
TAS4464
currently
entered
into
clinical
trials
for
cancer
therapy,
particularly
hematological
tumors.
This
review
explains
relationships
between
cancers,
structural
characteristics
multistep
mechanisms
NEDD8
by
NAE.
In
addition,
potential
approaches
discover
detailed
pharmacological
stage
are
explored
depth.
Importantly,
we
reasonably
investigate
challenges
therapy
possible
development
directions
NAE-targeting
drugs
future.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Янв. 26, 2024
Abstract
Accumulation
of
senescent
cells
with
age
leads
to
tissue
dysfunction
and
related
diseases.
Their
detection
in
vivo
still
constitutes
a
challenge
aging
research.
We
describe
the
generation
fluorogenic
probe
(sulfonic-Cy7Gal)
based
on
galactose
derivative,
serve
as
substrate
for
β-galactosidase,
conjugated
Cy7
fluorophore
modified
sulfonic
groups
enhance
its
ability
diffuse.
When
administered
male
or
female
mice,
β-galactosidase
cleaves
O-glycosidic
bond,
releasing
that
is
ultimately
excreted
by
kidneys
can
be
measured
urine.
The
intensity
recovered
reliably
reflects
an
experimentally
controlled
load
cellular
senescence
correlates
age-associated
anxiety
during
senolytic
treatment.
Interestingly,
our
findings
indicate
effects
senolysis
are
temporary
if
treatment
discontinued.
Our
strategy
may
basis
developing
platforms
designed
easy
longitudinal
monitoring
enzymatic
activities
biofluids.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(7), С. 4031 - 4031
Опубликована: Апрель 4, 2024
The
tumor
microenvironment
(TME)
plays
an
essential
role
in
progression
and
modulating
response
to
anticancer
therapy.
Cellular
senescence
leads
a
switch
the
cell
secretome,
characterized
by
senescence-associated
secretory
phenotype
(SASP),
which
may
regulate
tumorigenesis.
Senolytic
therapy
is
considered
novel
strategy
that
eliminates
deleterious
effects
of
senescent
cells
TME.
Here,
we
show
two
different
types
senolytic
drugs,
despite
efficiently
depleting
cells,
have
opposite
on
cancer-associated
fibroblasts
(CAFs)
their
ability
epithelial-mesenchymal
transition
(EMT).
We
found
navitoclax
combination
dasatinib/quercetin,
reduced
number
spontaneously
TNF-induced
CAFs.
Despite
depletion
dasatinib/quercetin
versus
increased
secretion
SASP
pro-inflammatory
cytokine
IL-6.
This
differential
effect
correlated
with
promotion
enhanced
migration
EMT
MC38
colorectal
cancer
cells.
Our
results
demonstrate
some
senolytics
side
unrelated
activity
promote
argue
for
more
careful
extensive
studies
various
aspects
resistance
before
implemented
clinic.
ACS Nano,
Год журнала:
2024,
Номер
18(9), С. 7011 - 7023
Опубликована: Фев. 23, 2024
Ferroptotic
cancer
therapy
has
been
extensively
investigated
since
the
genesis
of
ferroptosis
concept.
However,
therapeutic
efficacy
induction
in
heterogeneous
and
plastic
melanoma
compromised,
because
melanocytic
transitory
cell
subpopulation
is
resistant
to
iron-dependent
oxidative
stress.
Here,
we
report
a
phenotype-altering
liposomal
nanomedicine
enable
ferroptosis-resistant
subtypes
cells
vulnerable
lipid
peroxidation
via
senescence
induction.
The
strategy
involves
ratiometric
coencapsulation
cyclin-dependent
kinase
4
6
(CDK4/6)
inhibitor
(palbociclib)
inducer
(auranofin)
within
cRGD
peptide-modified
targeted
liposomes.
two
drugs
showed
synergistic
anticancer
effect
model
B16F10
cells,
as
evidenced
by
combination
index
analysis
(<1).
liposomes
could
efficiently
deliver
both
into
manner.
Afterward,
potently
induced
intracellular
redox
imbalance
peroxidation.
Palbociclib
significantly
provoked
cycle
arrest
at
G0/G1
phase,
which
sensitized
auranofin-caused
through
Meanwhile,
palbociclib
depleted
glutathione
(GSH)
reduced
nicotinamide
adenine
dinucleotide
phosphate
(NADPH),
further
boosting
ferroptosis.
proof-of-concept
was
also
demonstrated
tumor-bearing
mice
model.
current
work
offers
promising
ferroptosis-targeting
for
effectively
treating
manipulating
cellular
plasticity.
Abstract
In
situ
precise
detection
of
bioactive
molecules
with
high
sensitivity
and
spatiotemporal
resolution
is
essential
for
studying
physiological
events
disease
diagnosis.
The
utilization
versatile
fluorescent
probes
in
fluorescence
imaging
offers
a
powerful
tool
vivo
biomarkers
closely
associated
pathological
conditions.
However,
the
dynamic
behavior
leading
to
rapid
clearance
small
molecule
from
regions
interest
severely
compromises
their
potential
imaging.
Notably,
self‐immobilizing
that
selectively
recognize
diseased
tissues
while
improving
retention
enrichment
enable
accurate
high‐fidelity
this
review,
we
aim
summarize
strategies
employed
recent
advances
performance
precision
using
techniques.
Lastly,
discuss
prospects
challenges
promote
further
development
application
more
delicate
probes.
