Abstract
Cuproptosis
is
a
newly
discovered
form
of
programmed
cell
death
significantly
depending
on
the
transport
efficacy
copper
(Cu)
ionophores.
However,
existing
Cu
ionophores,
primarily
small
molecules
with
short
blood
half‐life,
face
challenges
in
transporting
enough
amounts
ions
into
tumor
cells.
This
work
describes
construction
carrier‐free
nanoparticles
(Ce6@Cu
NPs),
which
self‐assembled
by
coordination
2+
sonosensitizer
chlorin
e6
(Ce6),
facilitating
sonodynamic‐triggered
combination
cuproptosis
and
ferroptosis.
Ce6@Cu
NPs
internalized
U87MG
cells
induce
sonodynamic
effect
glutathione
(GSH)
depletion
capability,
promoting
lipid
peroxidation
eventually
inducing
Furthermore,
+
concentration
increases
as
reacts
reductive
GSH,
resulting
downregulation
ferredoxin‐1
lipoyl
synthase.
induces
oligomerization
lipoylated
dihydrolipoamide
S‐acetyltransferase,
causing
proteotoxic
stress
irreversible
cuproptosis.
possess
satisfactory
ability
to
penetrate
blood‐brain
barrier,
significant
accumulation
orthotopic
U87MG‐Luc
glioblastoma.
The
ferroptosis
evidenced
both
vitro
vivo
minimal
side
effects.
represents
promising
therapeutic
strategy
combining
cuproptosis,
potentially
inspiring
further
research
developing
logical
effective
cancer
therapies
based
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.
Advanced Materials,
Год журнала:
2024,
Номер
36(45)
Опубликована: Сен. 17, 2024
Abstract
The
overexpression
of
polyamines
in
tumor
cells
contributes
to
the
establishment
immunosuppressive
microenvironment
and
facilitates
growth.
Here,
it
have
ingeniously
designed
multifunctional
copper‐piceatannol/HA
nanopills
(Cu‐Pic/HA
NPs)
that
effectively
cause
total
intracellular
depletion
by
inhibiting
synthesis,
depleting
polyamines,
impairing
uptake,
resulting
enhanced
pyroptosis
cuproptosis,
thus
activating
a
powerful
immune
response
achieve
anti‐tumor
therapy.
Mitochondrial
dysfunction
from
overall
not
only
leads
surge
copper
ions
mitochondria,
thereby
causing
aggregation
toxic
proteins
induce
but
also
triggers
accumulation
reactive
oxygen
species
(ROS)
within
which
further
upregulates
expression
zDHHC5
zDHHC9
promote
palmitoylation
gasdermin
D
(GSDMD)
GSDMD‐N,
ultimately
inducing
pyroptosis.
Then
occurrence
cuproptosis
is
conductive
remodel
microenvironment,
responses
growth
metastasis.
This
therapeutic
strategy
through
comprehensive
provides
novel
template
for
cancer
immunotherapy.
ACS Nano,
Год журнала:
2024,
Номер
18(19), С. 12386 - 12400
Опубликована: Май 3, 2024
Current
cancer
vaccines
face
challenges
due
to
an
immunosuppressive
tumor
microenvironment
and
their
limited
ability
produce
effective
immune
response.
To
address
the
above
limitations,
we
develop
a
3-(2-spiroadamantyl)-4-methoxy-4-(3-phosphoryloxy)-phenyl-1,2-dioxetane
(alkaline
phosphatase
substrate)
XMD8-92
(extracellular
signal-regulated
kinase
5
inhibitor)-codelivered
copper-tetrahydroxybenzoquinone
(Cu-THBQ/AX)
nanosized
metal–organic
framework
in
situ-generate
therapeutic
vaccination.
Once
inside
early
endosome,
alkaline
overexpressed
cells'
membrane
activates
situ
type
I
photodynamic
effect
of
Cu-THBQ/AX
for
generating
•O2–,
catalyzes
O2
H2O2
•O2–
•OH
via
semiquinone
radical
catalysis
Fenton-like
reactions.
This
surge
ROS
endosomes
triggers
caspase-3-mediated
proinflammatory
pyroptosis
activating
phospholipase
C.
Meanwhile,
can
also
induce
oligomerization
dihydrolipoamide
S-acetyltransferase
trigger
cell
cuproptosis.
The
production
could
release
effectively
inhibiting
efferocytosis
macrophages
convert
apoptosis
cells
into
secondary
necrosis.
simultaneous
induction
pyroptosis,
cuproptosis,
necrosis
converts
from
"cold"
"hot"
conditions,
making
it
antigen
pool.
transformation
successfully
antitumor
response,
growth
metastasis.
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 24, 2025
Photodynamic
therapy
(PDT)
holds
promise
as
a
cancer
treatment
modality
due
to
its
potential
for
enhanced
precision
and
safety.
To
enhance
deep
tissue
penetration
minimize
adsorption
phototoxicity,
developing
photosensitizers
activated
by
second
near-infrared
window
(NIR-II)
light
shows
significant
potential.
However,
the
efficacy
of
PDT
is
often
impeded
tumor
microenvironment
hypoxia,
primarily
caused
irregular
vasculature.
Fortunately,
stimulator
interferon
genes
(STING)
pathway,
known
immune
activation,
has
been
linked
vasculature
normalization.
In
this
study,
we
developed
nanoplatform
(Fe-THBQ/SR)
loading
STING
agonist
(SR-717)
into
an
iron-tetrahydroxy-1,4-benzoquinone
(Fe-THBQ)
metal–organic
framework.
Fe-THBQ
was
proven
be
effective
NIR-II
photosensitizer,
generating
numerous
reactive
oxygen
species
(ROS)
under
1064
nm
laser
irradiation.
These
ROS
downregulated
heat
shock
protein
expression,
consequently
promoting
mild-photothermal
(mild-PTT),
facilitated
ferroptosis
depleting
glutathione
(GSH)/glutathione
peroxidase
4.
Moreover,
Fe-THBQ/SR
released
SR-717
upon
GSH
stimulation,
synergizing
with
ROS-mediated
double-stranded
DNA
leakage
activation.
This
process
contributed
normalization
hypoxia
alleviation,
thereby
enhancing
efficacy.
Overall,
presented
versatile
single-laser-triggered
mild-PTT
simultaneously
coupled
it
activation
form
reinforcing
cycle.
synergistic
enhancements
increased
immunogenicity
cells,
remodeled
immunosuppressive
microenvironment,
T
lymphocyte
infiltration,
improved
therapeutic
outcomes.
International Journal of Biological Macromolecules,
Год журнала:
2024,
Номер
265, С. 130960 - 130960
Опубликована: Март 20, 2024
Tumors
remain
one
of
the
major
threats
to
public
health
and
there
is
an
urgent
need
design
new
pharmaceutical
agents
for
their
diagnosis
treatment.
In
recent
years,
due
rapid
development
nanotechnology,
biotechnology,
catalytic
science,
theoretical
computing,
subtlety
has
gradually
made
great
progress
in
research
related
tumor
Compared
conventional
drugs,
enzymes
can
improve
drug
distribution
enhance
enrichment
at
site,
thereby
reducing
side
effects
enhancing
efficacy.
Nanozymes
also
be
used
as
tracking
imaging
reshape
microenvironment,
providing
a
versatile
platform
treatment
malignancies.
this
paper,
we
review
current
status
on
oncology
analyze
novel
therapeutic
approaches
mechanisms.
To
date,
large
number
nanomaterials,
such
noble
metal
nonmetallic
carbon-based
have
been
shown
able
function
like
natural
enzymes,
particularly
with
significant
advantages
therapy.
light
this,
authors
systematically
summarized
evaluated
construction,
enzymatic
activity,
characteristics
nanozymes
respect
modalities
addition,
application
different
types
nicknames
features
years
are
detail.
We
conclude
summary
outlook
study
It
hoped
that
will
inspire
researchers
fields
chemistry,
biology,
materials
science
contribute
nano-enzymology.
Advanced Healthcare Materials,
Год журнала:
2024,
Номер
unknown
Опубликована: Май 9, 2024
Mild
photothermal
therapy
(PTT)
is
a
spatiotemporally
controllable
method
that
utilizes
the
effect
at
relatively
low
temperatures
(40-45
°C)
to
especially
eliminate
tumor
tissues
with
negligible
side
effects
on
surrounding
normal
tissues.
However,
overexpression
of
heat
shock
protein
70
(HSP70)
and
limited
single
treatment
drastically
impede
therapeutic
efficacy.
Herein,
constructed
multifunctional
core-shell
structured
Ag-Cu@SiO
Cellular & Molecular Biology Letters,
Год журнала:
2024,
Номер
29(1)
Опубликована: Июнь 25, 2024
Abstract
Cuproptosis,
a
newly
identified
copper
(Cu)-dependent
form
of
cell
death,
stands
out
due
to
its
distinct
mechanism
that
sets
it
apart
from
other
known
death
pathways.
The
molecular
underpinnings
cuproptosis
involve
the
binding
Cu
lipoylated
enzymes
in
tricarboxylic
acid
cycle.
This
interaction
triggers
enzyme
aggregation
and
proteotoxic
stress,
culminating
death.
specific
has
yet
be
fully
elucidated.
recognized
sparked
numerous
investigations
into
role
tumorigenesis
cancer
therapy.
In
this
review,
we
summarized
current
knowledge
on
metabolism
link
cancer.
Furthermore,
delineated
mechanisms
roles
cuproptosis-related
genes
Finally,
offered
comprehensive
discussion
most
recent
advancements
ionophores
nanoparticle
delivery
systems
utilize
as
cutting-edge
strategy
for
treatment.
