Molecular Pharmaceutics,
Journal Year:
2024,
Volume and Issue:
22(1), P. 209 - 220
Published: Dec. 10, 2024
Positron
emission
tomography
(PET)
is
a
promising
modality
for
early
diagnosis,
accurate
detection,
and
staging
of
hepatocellular
carcinoma
(HCC).
Hereby,
dual-specific
probe
targeting
Glypican-3
(GPC3)
prostate-specific
membrane
antigen
(PSMA)
was
evaluated
HCC
PET
imaging.
The
prepared
by
conjugating
TJ12P2,
GPC3-targeting
peptide
previously
reported
our
group,
to
highly
potent
PSMA
inhibitor
via
polyethylene
glycol
linker
further
tethered
the
1,4,7-triazacyclononane-1,4,7-triacetic
acid
(NOTA)
chelator.
resultant
probe,
NOTA-TJ12P2-PSMA,
abbreviated
as
T2P,
labeled
with
gallium-68
fluorine-18,
respectively,
in
murine
models
various
levels
GPC3
expression.
Targeting
specificity
confirmed
blocking
studies.
synthesized
[
Research Square (Research Square),
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 2, 2025
Abstract
Mitophagy
is
crucial
for
the
selective
autophagic
degradation
of
damaged
mitochondria,
helping
to
maintain
both
mitochondrial
and
cellular
homeostasis.
Here,
we
report
a
fluoroalkylated
polypyridinium
that
specifically
targets
mitochondria
exhibits
high
activity
in
mitophagy
induction.
The
polymer
effectively
restores
function
alleviates
inflammatory
response
foam
cells
by
activating
mitophagy,
displays
inherent
red
fluorescence
under
physiological
conditions,
allowing
direct
tracing
its
biodistribution
in
vivo.
Besides,
nanoparticle
shows
serum
stability
due
antifouling
properties
fluoroalkyl
tags.
After
intravenous
administration,
reduces
oxidative
stress,
promotes
decreases
senescence
atherosclerotic
plaques,
contributing
therapeutic
efficacy.
This
study
presents
novel
effective
strategy
treatment
atherosclerosis
other
dysfunction-related
conditions.
Small,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 24, 2025
Abstract
Tumor
tissues
exhibit
elevated
oxidative
stress,
with
the
cystine‐glutamate
transporter
x
CT
solute
carrier
family
7
member
11
(
CT/SLC7A11)
protecting
cancer
cells
from
damage
by
facilitating
cystine
uptake
for
glutathione
synthesis.
Disulfidptosis,
a
newly
identified
form
of
programmed
cell
death
(PCD),
occurs
in
high
CT/SLC7A11
expression
under
glucose‐deprived
conditions.
Distinct
other
PCD
pathways,
disulfidptosis
is
characterized
aberrant
disulfide
bond
formation
and
cellular
dysfunction,
ultimately
resulting
death.
This
novel
mechanism
offers
remarkable
therapeutic
potential
targeting
inherent
stress
vulnerabilities
rapidly
growing
cells.
Advances
nanotechnology
enable
development
nanomaterials
capable
inducing
reactive
oxygen
species
(ROS)
generation,
disrupting
bonds.
In
addition,
they
are
to
deliver
agents
directly
tumors,
thereby
improving
precision
minimizing
off‐target
effects.
Moreover,
combining
ROS‐induced
immunogenic
can
remodel
tumor
microenvironment
enhance
anti‐tumor
immunity.
review
explores
mechanisms
underlying
disulfidptosis,
its
treatment,
synergistic
role
amplifying
Selective
induction
using
represents
promising
strategy
achieving
more
effective,
selective,
less
toxic
therapies.
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
67(8), P. 6726 - 6737
Published: April 3, 2024
Cyclin-dependent
kinase
19
(CDK19)
is
overexpressed
in
prostate
cancer,
making
it
an
attractive
target
for
both
imaging
and
therapy.
Since
little
known
about
the
optimized
approach
radioligands
of
nuclear
proteins,
linker
optimization
strategies
were
used
to
improve
pharmacokinetics
tumor
absorption,
including
adjustment
length,
flexibility/rigidity,
hydrophilicity/lipophilicity
linkers.
Molecular
docking
was
conducted
virtual
screening
followed
by
IC50
determination.
Both
BALB/c
mice
P-16
xenografts
tissue
distribution
PET/CT
imaging.
The
ligand
68Ga-10c
demonstrated
high
absorption
5
min
after
injection
sustains
long-term
within
3
h.
Furthermore,
exhibited
slow
clearance
predominantly
metabolized
liver
kidneys,
showing
potential
alleviate
metabolic
pressure
enhance
safety.
Therefore,
strategy
well
suited
CDK19
provides
a
reference
radioactive
ligands
other
targets.
Advanced Functional Materials,
Journal Year:
2024,
Volume and Issue:
34(36)
Published: April 25, 2024
Abstract
Chimeric
antigen
receptor
(CAR)‐T
cell
therapy
has
demonstrated
poor
efficacy
for
solid
tumors.
The
low
number
and
functional
persistence
of
CAR‐T
cells
in
tumors
are
the
main
limiting
factors.
Here
a
C
hemokine‐based
I
njectable
platform
enhancing
adoptive
T
cells’
E
fficacy
(CITE)
is
presented.
CITE
consists
peritumorally‐injected
immunogel
co‐loading
chemotactic
CXCL9
particles
with
PD‐1
antibody
(aPD1)
intravenously‐infused
tumor‐penetrating
peptide
iRGD.
Immunogel
formed
drug
depots
allowed
sustained
release
cargo
peritumorally
while
iRGD
facilitated
tumor
infiltration
gel‐released
drugs,
thus
remarkably
increasing
amount
aPD1
tumor.
induced
an
effective
gradient
to
promote
tumor‐specific
migration
boosted
function
infiltrated
by
blocking
immunosuppression
via
two‐in‐one
approach.
Consequently,
yielded
218‐fold
increase
intratumoral
transferred
substantially
improved
efficacies
(TCR)‐T
multiple
syngeneic
models,
including
immunologically
“cold”
tumors,
immunocompetent
mice.
More
importantly,
enhanced
systemic
antitumor
immunity
elicited
immune
memory,
enabling
treat
multimodal,
metastatic,
recurrent
broadly
applicable
therapies
involving
or
TCR‐T
cells.
Biomedicine & Pharmacotherapy,
Journal Year:
2024,
Volume and Issue:
177, P. 117063 - 117063
Published: July 4, 2024
Off-targeting
toxicity
and
immunosuppressive
tumor
microenvironment
still
restrict
the
therapeutic
requirement
of
photodynamic
therapy
(PDT).
The
development
metal
ion-coordination-based
nanoparticles
(NPs)
for
cancer
has
advantages,
such
as
precious
nanostructure
potent
effect
well
great
safety.
In
this
study,
we
prepared
calcium
ions
(Ca
Cancers,
Journal Year:
2024,
Volume and Issue:
16(18), P. 3120 - 3120
Published: Sept. 10, 2024
Purpose:
To
investigate
the
impact
of
physiologically
based
pharmacokinetic
(PBPK)
parameters
on
physical,
biological,
and
statistical
measures
in
lutetium-177-labeled
radiopharmaceutical
therapies
(RPTs)
targeting
prostate-specific
membrane
antigen
(PSMA).
Methods:
Using
a
clinically
validated
PBPK
model,
realistic
time–activity
curves
(TACs)
for
tumors,
salivary
glands,
kidneys
were
generated
various
model
parameters.
These
TACs
used
to
calculate
area-under-the-TAC
(AUC),
dose,
biologically
effective
dose
(BED),
figure-of-merit
BED
(fBED).
The
effects
these
radiobiological,
pharmacokinetic,
time,
features
assessed.
Results:
Manipulating
significantly
influenced
AUC,
BED,
fBED
outcomes
across
four
different
models.
Higher
association
rates
increased
values
with
minimal
non-target
organs.
Increased
internalization
reduced
AUC
tumors
kidneys.
serum
protein-binding
decreased
all
tissues.
Elevated
tumor
receptor
density
ligand
amounts
enhanced
uptake
effectiveness
tumors.
Larger
volumes
required
dosimetry
adjustments
maintain
efficacy.
Setting
release
rate
zero
intensified
rates,
enhancing
while
minimizing
glands
Conclusions:
Optimizing
can
enhance
efficacy
RPTs
PSMA,
providing
insights
personalized
treatment
regimens
minimize
toxicity
improve
therapeutic
outcomes.
ACS Pharmacology & Translational Science,
Journal Year:
2024,
Volume and Issue:
7(12), P. 4021 - 4031
Published: Nov. 26, 2024
Hepatocellular
carcinoma
(HCC)
represents
the
predominant
form
of
primary
liver
cancer,
yet
early,
precise,
and
noninvasive
detection
continues
to
pose
a
considerable
clinical
challenge.
Glypican-3
(GPC3),
membrane-bound
proteoglycan,
is
markedly
overexpressed
in
most
HCC
cases,
while
exhibiting
low
expression
normal
hepatitis-affected
tissues.
Given
its
crucial
role
malignant
transformation
tumor
progression,
GPC3
emerges
as
compelling
target
for
imaging.
In
this
study,
we
developed
evaluated
2
68Ga-labeled
GPC3-targeted
positron
emission
tomography
(PET)
probes,
each
incorporating
either
polyethylene
glycol
(PEG)
or
4-(p-methylphenyl)butanoic
acid
(an
albumin-binding
moiety).
Comparative
analyses
revealed
that
68Ga-ALB-GBP,
which
includes
moiety,
exhibited
superior
vivo
stability,
enhanced
uptake,
an
improved
tumor-to-liver
ratio
relative
68Ga-PEG2-GBP
subcutaneous
mouse
models.
Micro-PET/computed
imaging
orthotopic
cancer
with
68Ga-ALB-GBP
demonstrated
2.29
±
0.13
tumor-to-muscle
13.03
1.63
at
3
h
postinjection,
outperforming
performance
clinically
used
18F-fluorodeoxyglucose
PET
These
findings
suggest
promising
diagnostic
tool
strong
candidate
translation
potential
utility
both
therapeutic
settings.
Moreover,
incorporation
moiety
into
tracers
significantly
extends
blood
circulation
time,
thereby
enhancing
bioavailability
facilitating
high-contrast
Molecular Pharmaceutics,
Journal Year:
2024,
Volume and Issue:
22(1), P. 209 - 220
Published: Dec. 10, 2024
Positron
emission
tomography
(PET)
is
a
promising
modality
for
early
diagnosis,
accurate
detection,
and
staging
of
hepatocellular
carcinoma
(HCC).
Hereby,
dual-specific
probe
targeting
Glypican-3
(GPC3)
prostate-specific
membrane
antigen
(PSMA)
was
evaluated
HCC
PET
imaging.
The
prepared
by
conjugating
TJ12P2,
GPC3-targeting
peptide
previously
reported
our
group,
to
highly
potent
PSMA
inhibitor
via
polyethylene
glycol
linker
further
tethered
the
1,4,7-triazacyclononane-1,4,7-triacetic
acid
(NOTA)
chelator.
resultant
probe,
NOTA-TJ12P2-PSMA,
abbreviated
as
T2P,
labeled
with
gallium-68
fluorine-18,
respectively,
in
murine
models
various
levels
GPC3
expression.
Targeting
specificity
confirmed
blocking
studies.
synthesized
[
