Frontiers in Pharmacology,
Год журнала:
2025,
Номер
15
Опубликована: Янв. 10, 2025
Breast
cancer
is
the
most
commonly
diagnosed
worldwide.
Metal
metabolism
pivotal
for
regulating
cell
fate
and
drug
sensitivity
in
breast
cancer.
Iron
copper
are
essential
metal
ions
critical
maintaining
cellular
function.
The
accumulation
of
iron
triggers
distinct
death
pathways,
known
as
ferroptosis
cuproptosis,
respectively.
Ferroptosis
characterized
by
iron-dependent
lipid
peroxidation,
while
cuproptosis
involves
copper-induced
oxidative
stress.
They
increasingly
recognized
promising
targets
development
anticancer
drugs.
Recently,
compelling
evidence
demonstrated
that
interplay
between
plays
a
crucial
role
progression.
This
review
elucidates
converging
pathways
Moreover,
we
examined
value
genes
associated
with
clinical
diagnosis
treatment
cancer,
mainly
outlining
potential
co-targeting
approach.
Lastly,
delve
into
current
challenges
limitations
this
strategy.
In
general,
offers
an
overview
interaction
offering
valuable
perspectives
further
research
treatment.
Abstract
Cuproptosis
is
an
emerging
cell
death
pathway
that
depends
on
the
intracellular
Cu
ions.
Elesclomol
(ES)
as
efficient
ionophore
can
specifically
transport
into
mitochondria
and
trigger
cuproptosis.
However,
ES
be
rapidly
removed
metabolized
during
intravenous
administration,
leading
to
a
short
half‐life
limited
tumor
accumulation,
which
hampers
its
clinical
application.
Here,
study
develops
reactive
oxygen
species
(ROS)‐responsive
polymer
(PCP)
based
cinnamaldehyde
(CA)
polyethylene
glycol
(PEG)
encapsulate
ES‐Cu
compound
(EC),
forming
ECPCP.
ECPCP
significantly
prolongs
systemic
circulation
of
EC
enhances
accumulation.
After
cellular
internalization,
PCP
coating
stimulatingly
dissociates
exposing
high‐level
ROS,
releases
Cu,
thereby
triggering
via
Meanwhile,
2+
‐stimulated
Fenton‐like
reaction
together
with
CA‐stimulated
ROS
production
simultaneously
breaks
redox
homeostasis,
compensates
for
insufficient
oxidative
stress
treated
alone,
in
turn
inducing
immunogenic
cells,
achieving
simultaneous
cuproptosis
immunotherapy.
Furthermore,
excessive
accelerates
stimuli‐dissociation
ECPCP,
positive
feedback
therapy
loop
against
self‐alleviation.
Therefore,
nanoplatform
immunotherapy
improves
dual
antitumor
mechanism
provides
potential
optimization
Journal of Hematology & Oncology,
Год журнала:
2024,
Номер
17(1)
Опубликована: Авг. 16, 2024
Cuproptosis
is
a
newly
identified
form
of
cell
death
induced
by
excessive
copper
(Cu)
accumulation
within
cells.
Mechanistically,
cuproptosis
results
from
Cu-induced
aggregation
dihydrolipoamide
S-acetyltransferase,
correlated
with
the
mitochondrial
tricarboxylic
acid
cycle
and
loss
iron–sulfur
cluster
proteins,
ultimately
resulting
in
proteotoxic
stress
triggering
death.
Recently,
has
garnered
significant
interest
tumor
research
due
to
its
potential
as
crucial
therapeutic
strategy
against
cancer.
In
this
review,
we
summarized
cellular
molecular
mechanisms
relationship
other
types
Additionally,
reviewed
current
drugs
or
strategies
available
induce
cells,
including
Cu
ionophores,
small
compounds,
nanomedicine.
Furthermore,
targeted
metabolism
specific
regulatory
genes
cancer
therapy
enhance
sensitivity
cuproptosis.
Finally,
discussed
feasibility
targeting
overcome
chemotherapy
immunotherapy
resistance
suggested
future
directions.
This
study
that
could
open
new
avenues
for
developing
therapy.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(44), С. 30033 - 30045
Опубликована: Окт. 28, 2024
Cuproptosis,
a
recently
identified
form
of
copper-dependent
cell
death,
shows
promising
tumor
suppressive
effects
with
minimal
drug
resistance.
However,
its
therapeutic
efficacy
is
hampered
by
dependence
on
copper
ions
and
the
glutathione
(GSH)-rich
microenvironment
in
tumors.
Here,
we
have
developed
polyvalent
aptamer
nanodrug
conjugates
(termed
CuPEs@PApt)
nucleosome-like
structure
to
improve
cuproptosis
therapy
exploiting
mitochondrial
overload
GSH
depletion.
Polyvalent
(PApt),
comprising
epithelial
adhesion
molecule
aptamers
for
targeting
repetitive
PolyT
sequences
chelation,
facilitates
efficient
loading
targeted
delivery
peroxide-Elesclomol
nanodots
(CuPEs).
Upon
internalization
cells,
Elesclomol
released
from
CuPEs@PApt
accumulates
mitochondria
initiate
cuproptosis,
while
lysosomal
degradation
CuP
generates
exogenous
Cu2+
H2O2,
triggering
Fenton-like
reaction
depletion
enhance
cuproptosis.
In
vitro
vivo
experiments
confirm
this
strategy
inducing
immunogenic
latter
contributing
activation
antitumor
immune
response
synergistic
growth
inhibition.
Materials Horizons,
Год журнала:
2024,
Номер
11(18), С. 4275 - 4310
Опубликована: Янв. 1, 2024
This
comprehensive
review
systematically
summarizes
the
intrinsic
mechanism
of
different
metal
ion
(such
as
Fe
3+
/Fe
2+
,
Cu
/Cu
+
Ca
Zn
Mn
Na
/K
and
Mg
)-mediated
interference
therapies
their
research
progress
in
cancer
treatment.
Advanced Science,
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 16, 2024
The
combination
of
cuproptosis
and
immune
checkpoint
inhibition
has
shown
promise
in
treating
malignant
tumors.
However,
it
remains
a
challenge
to
deliver
copper
ions
inhibitors
efficiently
simultaneously
Herein,
mitochondria-targeted
nanoscale
coordination
polymer
particle,
Cu/TI,
comprising
Cu(II),
triphenylphosphonium
conjugate
5-carboxy-8-hydroxyquinoline
(TI),
for
effective
induction
programmed
cell
death-1
(PD-L1)
downregulation
is
reported.
Upon
systemic
administration,
Cu/TI
accumulates
tumor
tissues
induce
immunogenic
cancer
death
reduce
PD-L1
expression.
Consequently,
promotes
the
intratumoral
infiltration
activation
cytotoxic
T
lymphocytes
greatly
inhibit
progression
colorectal
carcinoma
triple-negative
breast
mouse
models
without
causing
obvious
side
effects.
Journal of Materials Chemistry B,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
This
review
discusses
the
recent
developments
in
copper-based
nanomaterials
that
utilize
copper-induced
cell
death,
categorized
by
materials
systems,
while
highlighting
limitations
of
current
cuproptosis
related
nanomaterials.
Advanced Therapeutics,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 3, 2025
Abstract
Copper
plays
a
pivotal
role
in
human
physiology,
particularly
oncology,
acting
both
as
facilitator
of
progression
and
also
potential
avenue
for
advanced
therapeutic
approaches.
Maintaining
copper
homeostasis
is
crucial.
The
dysregulation
implicated
tumor
growth
through
its
involvement
critical
processes
angiogenesis,
proliferation,
metastasis.
elevation
level
the
microenvironment
(TME)
activates
oncogenic
pathways
to
drive
neovascularization
sustained
malignancies.
However,
same
reliance
on
offers
unique
weakness
that
can
be
leveraged
innovative
interventions.
recent
advances
nanomedicine
enable
synthesis
nanostructures
help
modulate
with
precision
offering
multifaceted
approaches
copper‐based
cancer
therapy
controlled
release
mechanism,
optimized
structures
induce
cuproptosis,
selective
eradication
cells
minimum
systemic
toxicity.
This
review
explores
dual
biology,
emphasizing
contribution
tumors
emerging
application
targeted
therapy.
highlights
harnessing
therapies
their
transformative
from
bench
bed
side
novel,
highly
effective,
clinical
safety.
Cuproptosis,
a
distinct
cell
death
pathway,
has
been
integrated
into
nanomedicine
for
disease
theranostics.
However,
current
nanosystems
inducing
cuproptosis
rely
on
exogenous
toxic
copper
ions,
limiting
the
scope
of
biomaterials.
Developing
nanoplatforms
that
induce
without
holds
substantial
promise.
Here,
we
engineered
two-dimensional
iron
(Fe)
single-atom–doped
molybdenum
disulfide
(MoS
2
)
piezocatalyst
(Fe-MoS
tumor
therapy.
Incorporating
single
Fe
atoms
enhances
MoS
piezoelectric
polarization
via
charge
redistribution
and
modulates
Mo
oxidation
states,
enabling
multifaceted
enzymatic
activities,
including
peroxidase-,
glutathione
oxidase–,
oxidase-,
catalase-like
activities.
Upon
ultrasound
stimulation,
Fe-MoS
nanocatalyst
generates
reactive
oxygen
species
depletes
synergistic
piezocatalytic
enzyocatalytic
effects,
disrupting
ion
homeostasis
cuproptosis,
concurrently
triggering
ferroptosis
ferritinophagy,
which
collectively
suppression.
This
study
represents
first
paradigm
to
introduce
copper-free
initiating
substantially
advancing
applications
in
Nano Letters,
Год журнала:
2024,
Номер
24(43), С. 13708 - 13717
Опубликована: Окт. 17, 2024
Reactive
oxygen
species
(ROS)-responsive
drug
delivery
systems
possess
immense
potential
for
targeted
and
controlled
release
of
therapeutics.
However,
the
rapid
responsiveness
to
ROS
sustained
antibacterial
drugs
are
often
limited
by
challenging
microenvironment
periodontitis.
Integrating
ROS-responsive
with
photocatalytic
technologies
presents
a
strategic
approach
overcome
these
limitations.
Herein,
pillararene-embedded
covalent
organic
framework
(PCOF)
incorporating
prodrug
thioacetal
(TA)
has
been
developed
treat
This
drug-loaded
nanoplatform,
namely
TA-loaded
PCOF,
utilizes
self-amplifying
property
enhance
therapeutic
efficacy.
PCOFs
demonstrate
exceptional
photosensitivity
generation
capabilities
when
employed
as
carriers.
When
exposed
ROS,
TA
within
nanoplatform
was
activated
cleaved
into
cinnamaldehyde
(CA),
highly
potent
compound.
By
leveraging
visible
light
activate
site-specific
infection
targeting,
PCOF
effectively
alleviated
periodontitis,
thereby
advancing
field
systems.