Advanced Materials,
Год журнала:
2023,
Номер
35(22)
Опубликована: Март 14, 2023
Cuproptosis
is
a
new
cell
death
that
depends
on
copper
(Cu)
ionophores
to
transport
Cu
into
cancer
cells,
which
induces
death.
However,
existing
are
small
molecules
with
short
blood
half-life
making
it
hard
enough
cells.
Herein,
reactive
oxygen
species
(ROS)-sensitive
polymer
(PHPM)
designed,
used
co-encapsulate
elesclomol
(ES)
and
form
nanoparticles
(NP@ESCu).
After
entering
ES
Cu,
triggered
by
excessive
intracellular
ROS,
readily
released.
work
in
concerted
way
not
only
kill
cells
cuproptosis,
but
also
induce
immune
responses.
In
vitro,
the
ability
of
NP@ESCu
efficiently
cuproptosis
investigated.
addition,
change
transcriptomes
treated
explored
RNA-Seq.
vivo,
found
mice
model
subcutaneous
bladder
cancer,
reprograming
tumor
microenvironment.
Additionally,
further
combined
anti-programmed
protein
ligand-1
antibody
(αPD-L1).
This
study
provides
first
report
combining
nanomedicine
can
αPD-L1
for
enhanced
therapy,
thereby
providing
novel
strategy
future
therapy.
Drug Resistance Updates,
Год журнала:
2023,
Номер
72, С. 101018 - 101018
Опубликована: Ноя. 11, 2023
Cuproptosis
is
a
newly
identified
form
of
cell
death
driven
by
copper.
Recently,
the
role
copper
and
triggered
in
pathogenesis
cancers
have
attracted
attentions.
has
garnered
enormous
interest
cancer
research
communities
because
its
great
potential
for
therapy.
Copper-based
treatment
exerts
an
inhibiting
tumor
growth
may
open
door
chemotherapy-insensitive
tumors.
In
this
review,
we
provide
critical
analysis
on
homeostasis
dysregulation
development
progression
cancers.
Then
core
molecular
mechanisms
cuproptosis
discussed,
followed
summarizing
current
understanding
copper-based
agents
(copper
chelators,
ionophores,
complexes-based
dynamic
therapy)
treatment.
Additionally,
summarize
emerging
data
ionophores
to
subdue
chemotherapy
resistance
different
types
We
also
review
small-molecule
compounds
nanoparticles
(NPs)
that
kill
cells
inducing
cuproptosis,
which
will
shed
new
light
anticancer
drugs
through
future.
Finally,
important
concepts
pressing
questions
future
should
be
focused
were
discussed.
This
article
suggests
targeting
could
novel
antitumor
therapy
strategy
overcome
drug
resistance.
ACS Nano,
Год журнала:
2023,
Номер
17(23), С. 23998 - 24011
Опубликована: Ноя. 21, 2023
Programmed
death-ligand
1
(PD-L1)
is
a
specialized
shield
on
tumor
cells
that
evades
the
immune
system.
Even
inhibited
by
PD-L1
antibodies,
cycling
process
constantly
transports
from
inside
to
outside
of
cells,
facilitating
renewal
and
replenishment
cancer
cell
membrane.
Herein,
we
develop
sodium
alginate
hydrogel
consisting
elesclomol-Cu
galactose
induce
persistent
cuproptosis,
leading
reduction
for
radio-immunotherapy
colon
tumors.
First,
prefabricated
synthesized
immobilizing
elesclomol
onto
saccharide
chain
through
coordination
with
bivalent
copper
ions
(Cu2+),
followed
incorporation
galactose.
After
implantation
into
tumors,
this
can
be
further
cross-linked
in
presence
physiological
calcium
(Ca2+),
resulting
formation
controlled
release
elesclomol-Cu2+
(ES-Cu)
The
effectively
induces
oligomerization
DLAT
cuproptosis
colorectal
cells.
Interestingly,
radiation-induced
upregulation
abrogated
hydrogel,
releasing
ES-Cu
Consequently,
sensitization
radiotherapy
immunotherapy
significantly
improved,
prolonging
survival
tumor-bearing
mice
both
local
metastatic
Our
study
introduces
an
approach
combines
radiotherapy.
Frontiers in Endocrinology,
Год журнала:
2023,
Номер
14
Опубликована: Март 6, 2023
Ovarian
cancer
(OC)
is
one
of
the
most
common
and
malignant
gynecological
malignancies
in
gynecology.
On
other
hand,
dysregulation
copper
metabolism
(CM)
closely
associated
with
tumourigenesis
progression.
Here,
we
investigated
impact
genes
(CMRGs)
on
prognosis
OC,
discovered
various
CM
clusters,
built
a
risk
model
to
evaluate
patient
prognosis,
immunological
features,
therapy
response.15
CMRGs
affecting
OC
patients
were
identified
The
Cancer
Genome
Atlas
(TCGA).
Consensus
Clustering
was
used
identify
two
clusters.
lasso-cox
methods
establish
metabolism-related
gene
prognostic
signature
(CMRGPS)
based
differentially
expressed
GSE63885
cohort
as
an
external
validation
cohort.
Expression
score-associated
verified
by
single-cell
sequencing
quantitative
real-time
PCR
(qRT-PCR).
Nomograms
visually
depict
clinical
value
CMRGPS.
Differences
traits,
immune
cell
infiltration,
tumor
mutational
load
(TMB)
between
groups
also
extensively
examined.
Tumour
Immune
Dysfunction
Rejection
(TIDE)
Phenotype
Score
(IPS)
validate
whether
CMRGPS
could
predict
response
immunotherapy
patients.In
TCGA
cohorts,
clusters
that
differed
significantly
terms
overall
survival
(OS)
microenvironment.
We
then
created
containing
11
confirmed
its
reliable
predictive
power
for
patients.
expression
score-related
validated
qRT-PCR.
Patients
divided
into
low-risk
(LR)
high-risk
(HR)
median
score,
better
LR
group.
5-year
AUC
reached
0.74.
Enrichment
analysis
showed
group
immune-related
pathways.
results
TIDE
IPS
group.Our
study,
therefore,
provides
valuable
tool
further
guide
management
tailor
treatment
offering
new
insights
individualized
treatment.
Frontiers in Oncology,
Год журнала:
2023,
Номер
13
Опубликована: Июнь 23, 2023
As
an
essential
nutrient,
copper’s
redox
properties
are
both
beneficial
and
toxic
to
cells.
Therefore,
leveraging
the
characteristics
of
copper-dependent
diseases
or
using
copper
toxicity
treat
copper-sensitive
may
offer
new
strategies
for
specific
disease
treatments.
In
particular,
concentration
is
typically
higher
in
cancer
cells,
making
a
critical
limiting
nutrient
cell
growth
proliferation.
Hence,
intervening
metabolism
cells
become
potential
tumor
treatment
strategy,
directly
impacting
metastasis.
this
review,
we
discuss
body
summarize
research
progress
on
role
promoting
inducing
programmed
death
Additionally,
elucidate
copper-related
drugs
treatment,
intending
provide
perspectives
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
Abstract
Cuproptosis,
an
emerging
form
of
programmed
cell
death,
has
received
tremendous
attention
in
cancer
therapy.
However,
the
efficacy
cuproptosis
remains
limited
by
poor
delivery
efficiency
copper
ion
carriers.
Herein,
complex
nanoparticles
(denoted
as
Cu(I)
NP)
are
developed
that
can
efficiently
deliver
into
cells
to
induce
cuproptosis.
NP
demonstrate
stimulus‐responsive
release
complexes,
which
results
mitochondrial
dysfunction
and
promotes
aggregation
lipoylated
dihydrolipoamide
S‐acetyltransferase
(DLAT),
leading
Notably,
not
only
cuproptosis,
but
also
elicit
robust
immune
responses
suppress
tumor
growth.
Overall,
this
study
provides
a
promising
strategy
for
cuproptosis‐based
