Aggregate,
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 8, 2025
ABSTRACT
Atomically
precise
gold
nanoclusters
(NCs),
possessing
characteristics
of
molecules
and
nanoparticles,
offer
a
promising
solution
to
the
challenges
faced
by
existing
pyroptosis
inducers.
Their
abilities
catalyze
generation
reactive
oxygen
species
enhance
radiosensitization
position
them
as
effective
agents
for
activating
pyroptosis.
However,
their
catalytic
efficiency
is
often
compromised
limited
geometrically
accessible
spaces
around
active
sites
lack
suitable
ligands.
Leveraging
exposed
metal
centers
in
mononuclear
organometallic
catalysts
tunable
ligand
NCs,
herein,
ethynylferrocene
(EFc)
was
utilized
amplify
peroxidase
(POD)‐like
activity
NCs
establishing
unshielded
center
electron
donor‐acceptor
interaction
between
EFc
Au
core.
The
resulting
8
Fe
2
with
excellent
POD‐mimicking
could
efficiently
trigger
inducing
intracellular
oxidative
stress.
Moreover,
potential
deplete
glutathione
enable
magnetic
resonance
imaging,
also
induce
ferroptosis
serve
diagnostic
tool
tumors.
All
these
processes
can
be
further
potentiated
X‐ray
radiation,
taking
advantage
high
atomic
number
gold.
This
work
opens
new
avenues
engineering
properties
broadens
applications
biomedicine.
Advanced Functional Materials,
Journal Year:
2024,
Volume and Issue:
34(29)
Published: Feb. 23, 2024
Abstract
Autophagy,
a
lysosome‐involved
degradation
pathway,
as
self‐protective
cellular
process,
always
weakens
the
efficiency
of
tumor
therapies.
Herein,
for
first
time,
biodegradable
copper
(Cu)
ions
doped
layered
double
hydroxide
(Cu‐LDH)
nanoparticles
are
reported
cancer
immunotherapy
via
lysosomal
rupture‐mediated
“Broken
Window
Effect”.
Only
injection
Cu‐LDH
single
therapeutic
agent
achieves
various
organelles
destruction
after
rupture,
well
abnormal
aggregation
Cu
in
cells
cuproptosis
and
pyroptosis.
More
importantly,
autophagy
inhibition
caused
by
rupture
improves
overload‐mediated
pyroptosis
blocking
lysosome‐mediated
bulk
leading
to
good
anti‐tumor
immune
responses
ultimately
high‐efficiency
growth
inhibition.
This
Effect”
provides
new
paradigm
enhanced
therapy.
Nanoscale,
Journal Year:
2024,
Volume and Issue:
16(9), P. 4378 - 4391
Published: Jan. 1, 2024
Schematic
illustration
of
the
combinational
strategy
nanotechnology
and
PROTACs
(Nano-PROTACs):
typical
shortcomings
traditional
nanotechnology-based
strategies
for
PROTAC
drugs
optimization.
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
67(12), P. 10005 - 10011
Published: March 21, 2024
There
is
an
urgent
requirement
to
acquire
a
comprehensive
comprehension
of
novel
therapeutic
targets
for
prostate
cancer
facilitate
the
development
medications
with
innovative
mechanisms.
In
this
study,
we
identified
gambogic
acid
(GBA)
as
specific
pyroptosis
inducer
in
prostatic
cells.
By
using
thermal
proteome
profiling
(TPP)
strategy,
revealed
that
GBA
induces
by
directly
targeting
canopy
FGF
signaling
regulator
(CNPY3),
which
was
previously
considered
"undruggable".
Moreover,
through
utilization
APEX2-based
proximity
labeling
method,
found
recruited
delactatease
SIRT1,
resulting
elimination
lysine
lactylation
(Kla)
on
CNPY3.
Of
note,
SIRT1-mediated
delactylation
influenced
cellular
localization
CNPY3
promote
lysosome
rupture
triggering
pyroptosis.
Taken
together,
our
study
distinctive
target
induction
and
its
potential
application
therapy.
Molecular Cancer,
Journal Year:
2025,
Volume and Issue:
24(1)
Published: Jan. 17, 2025
Drug
resistance
is
a
common
challenge
in
clinical
tumor
treatment.
A
reduction
drug
sensitivity
of
cells
often
accompanied
by
an
increase
autophagy
levels,
leading
to
autophagy-related
resistance.
The
effectiveness
combining
chemotherapy
drugs
with
inducers/inhibitors
has
been
widely
confirmed,
but
the
mechanisms
are
still
unclear.
Ferroptosis
and
pyroptosis
can
be
affected
various
types
autophagy.
Therefore,
ferroptosis
have
crosstalk
via
autophagy,
potentially
switch
cell
death
under
certain
conditions.
As
two
forms
inflammatory
programmed
death,
different
effects
on
inflammation,
cGAS-STING
signaling
pathway
also
involved.
it
plays
important
role
progression
some
chronic
diseases.
This
review
discusses
relationship
between
pyroptosis,
attempts
uncover
reasons
behind
evasion
nature
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(12)
Published: Feb. 1, 2024
Pyroptosis
is
an
effective
anti-tumor
strategy.
However,
monometallic
pyroptosis
biotuners
have
not
been
explored
until
now.
Here,
we
discover
for
the
first
time
that
biodegradable
Al
can
act
as
a
biotuner
tumor
therapy.
pH-sensitive
nanoparticles
(Al@P)
are
obtained
by
equipping
polyethylene
glycol-b-(poly(methyl
methacrylate)-co-poly(4-vinylpyridine),
which
exert
their
effect
at
site
without
affecting
normal
cells.
The
H
Nano Letters,
Journal Year:
2024,
Volume and Issue:
24(28), P. 8741 - 8751
Published: July 2, 2024
The
degradation
of
oncoproteins
mediated
by
proteolysis-targeting
chimera
(PROTAC)
has
emerged
as
a
potent
strategy
in
cancer
therapy.
However,
the
clinical
application
PROTACs
is
hampered
challenges
such
poor
water
solubility
and
off-target
adverse
effects.
Herein,
we
present
an
ultrasound
(US)-activatable
PROTAC
prodrug
termed
NP
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Aug. 30, 2024
Due
to
low
success
rates
and
long
cycles
of
traditional
drug
development,
the
clinical
tendency
is
apply
omics
techniques
reveal
patient-level
disease
characteristics
individualized
responses
treatment.
However,
heterogeneous
form
data
uneven
distribution
targets
make
discovery
precision
medicine
a
non-trivial
task.
This
study
takes
pyroptosis
therapy
for
triple-negative
breast
cancer
(TNBC)
as
paradigm
uses
mining
large
TNBC
cohort
databases
establish
biofactor-regulated
neural
network
rapidly
screening
optimizing
compound
pairs.
Subsequently,
biomimetic
nanococrystals
are
prepared
using
preferred
combination
mitoxantrone
gambogic
acid
rational
delivery.
The
unique
mechanism
obtained
regulating
genes
through
ribosomal
stress
triggering
cascade
immune
effects
revealed
in
models.
In
this
work,
target
omics-based
intelligent
framework
explores
an
innovative
development
paradigm,
which
repurposes
existing
drugs
enables
precise
treatment
refractory
diseases.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(49)
Published: Aug. 24, 2024
Abstract
The
integration
of
pyroptosis
and
ferroptosis
hybrid
cell
death
induction
to
augment
immune
activation
represents
a
promising
avenue
for
anti‐tumor
treatment,
but
there
is
lack
research.
Herein,
we
developed
two
iridium
(III)‐triphenylamine
photosensitizers,
IrC
IrF
,
with
the
capacity
disrupt
redox
balance
induce
photo‐driven
cascade
damage
DNA
Kelch‐like
ECH‐associated
protein
1
(KEAP1).
absent
in
melanoma
2
(AIM2)‐related
cytoplasmic
nucleic
acid‐sensing
pathway,
triggered
by
damaged
DNA,
leads
gasdermin
D
(GSDMD)‐mediated
pyroptosis.
Simultaneously,
iron
homeostasis,
regulated
KEAP1/nuclear
factor
erythroid
2‐related
(NRF2)/heme
oxygenase
(HO‐1)
serves
as
pivotal
bridge,
facilitating
not
only
E
(GSDME)‐mediated
non‐canonical
pyroptosis,
also
synergy
glutathione
peroxidase
4
(GPX4)
depletion.
collaborative
action
generates
synergistic
effect
that
elicits
immunogenic
death,
stimulates
robust
response
effectively
inhibits
tumor
growth
vivo.
Our
work
introduces
first
metal‐based
small
molecule
dual‐inducers
potent
cancer
immunotherapy,
highlights
significance
homeostasis
vital
hub
connecting
effects
ferroptosis.
Chemical Society Reviews,
Journal Year:
2024,
Volume and Issue:
53(19), P. 9582 - 9608
Published: Jan. 1, 2024
Targeted
protein
degradation
(TPD)
has
emerged
as
a
revolutionary
paradigm
in
drug
discovery
and
development,
offering
promising
avenue
to
tackle
challenging
therapeutic
targets.
Unlike
traditional
approaches
that
focus
on
inhibiting
function,
TPD
aims
eliminate
proteins
of
interest
(POIs)
using
modular
chimeric
structures.
This
is
achieved
through
the
utilization
proteolysis-targeting
chimeras
(PROTACs),
which
redirect
POIs
E3
ubiquitin
ligases,
rendering
them
for
by
cellular
ubiquitin-proteasome
system
(UPS).
Additionally,
other
technologies
such
lysosome-targeting
(LYTACs)
autophagy-based
degraders
facilitate
transportation
endo-lysosomal
or
autophagy-lysosomal
pathways
degradation,
respectively.
Despite
significant
growth
preclinical
research,
many
fail
progress
beyond
this
stage
development.
Various
factors
contribute
limited
success
agents,
including
hurdle
inadequate
delivery
target
site.
Integrating
into
platforms
could
surmount
challenges