Applied Organometallic Chemistry,
Journal Year:
2024,
Volume and Issue:
39(1)
Published: Sept. 17, 2024
ABSTRACT
Copper
complexes
exhibit
promising
anticancer
properties,
which
can
be
further
promoted
by
suitable
ligands.
In
this
study,
we
synthesized
and
investigated
the
effects
of
three
copper(I)
with
N‐heterocyclic
carbene
(NHC)
ligands
derived
from
phenanthroline‐functionalized
imidazole
salts.
The
synthesis
these
NHC‐copper(I)
(
Cu1
‐
Cu3
)
was
meticulously
characterized
using
NMR
elemental
analysis;
their
crystal
structures
were
delineated
X‐ray
diffraction.
Our
findings
illustrate
unique
geometric
configurations
complexes:
features
a
dinuclear
arrangement
off‐linear
geometry;
Cu2
are
bi‐copper
core
stabilized
two
phenanthroline‐modified
Crucially,
in
vitro
cytotoxic
evaluations
revealed
that
possess
suitability
activity.
Among
them,
exhibited
enhanced
cytotoxicity
activity,
achieving
half‐maximal
inhibitory
concentration
(IC
50
4.36
±
0.25
μM
colon
cancer
cell
line
HCT‐116,
markedly
surpassing
efficacy
cisplatin.
Subsequent
investigations
elucidated
notably
increases
intracellular
reactive
oxygen
species
(ROS)
levels
induces
mitochondrial
membrane
depolarization
endoplasmic
reticulum
stress,
leading
to
oxidative
stress‐mediated
apoptosis
cells.
Being
a
recently
identified
mode
of
programmed
cell
demise,
the
functional
implications
cuproptosis
in
genesis,
progression,
and
therapeutic
modulation
cancer
remain
largely
unknown.
Given
that
is
predominantly
elicited
by
cellular
copper
overload,
notably
attributable
to
dysregulation
homeostasis
within
mitochondria,
we
designed
series
phosphorescent
rhenium(I)
complexes
(Re1-Re5)
as
suborganelle-targeted
ionophores.
Among
them,
Re5
can
successfully
transport
extracellular
into
mitochondria
Golgi
apparatus
especially
enrich
mitochondria.
Consequently,
breaks
redox
balance
disturbs
energetic
metabolism
pathways
induce
cuproptosis.
Finally,
prove
promote
immune
responses
modulate
microenvironments.
In
all,
present
here
first
subcellular
organelle-targeted
ionophore
cuproptosis-inducing
small
molecules
are
potent
immunotherapeutic
candidates.
Cuproptosis
is
a
new
copper-dependent
form
of
regulated
cell
death
and
shows
enormous
promise
in
cancer
therapy.
However,
its
therapeutic
performance
compromised
by
the
strictly
copper
metabolism
highly
expressed
intracellular
glutathione
(GSH).
Herein,
an
intelligent
nanoplatform
(NSeMON-P@CuT/LipD)
rationally
developed
as
metabolic
disrupter,
GSH
consumer,
Fenton-like
reaction
trigger
for
cuproptosis/ferroptosis/apoptosis
NSeMON-P@CuT/LipD
constructed
from
preparation
diselenide-bridged
mesoporous
organosilica
nanoparticles,
then
pemetrexed
(Pem)
loaded
followed
surface
deposition
with
Cu2+-3,3′-dithiobis(propionohydrazide)
(TPH)
coordinated
network
coating
diclofenac
(DC)-encapsulated
liposome.
In
response
to
specific
tumor
microenvironment,
obtained
can
release
DC,
Cu2+,
Pem
simultaneously
amplify
cellular
oxidative
stress
consuming
catalyzing
endogenous
H2O2
into
hydroxyl
radicals
(•OH).
Both
liberated
DC
augmented
inhibit
glycolysis,
reduce
ATP
level,
block
transporter
ATP7B,
resulting
disorders
high
retention
cells
•OH
generation.
Moreover,
overloaded
promote
dihydrolipoamide
S-acetyltransferase
oligomerization
Fe–S
cluster
protein
loss,
thus
evoking
cuproptosis.
Collectively,
activates
prominent
ferroptosis,
which
cooperates
cuproptosis
Pem-mediated
apoptosis
significantly
growth
4T1
tumor-bearing
mice.
This
study
demonstrates
feasible
strategies
enhance
using
single
may
also
inspire
design
advanced
cuproptosis-related
therapies.
Small,
Journal Year:
2023,
Volume and Issue:
20(14)
Published: Dec. 17, 2023
Copper-based
nanozymes
exhibit
excellent
antitumor
activity
but
are
easily
inactivated
due
to
the
disturbance
of
proteins
or
other
macromolecules
with
sulfhydryl.
A
tumor
microenvironment-responsive
CuMnO@Fe
Analytical Letters,
Journal Year:
2024,
Volume and Issue:
unknown, P. 1 - 14
Published: March 1, 2024
Accurate
detection
of
copper
ions
is
crucial
since
it
an
essential
trace
element.
Carbon
quantum
dots
(CQDs)
were
prepared
from
apricot
leaves
using
a
hydrothermal
method.
These
CQDs,
which
generated
reference
signal,
combined
with
glutathione-bound
gold
nanoclusters
(GSH-AuNCs)
synthesized
by
the
reduction
chloroauric
acid
to
form
ratiometric
fluorescent
probe.
The
probe
exhibited
fluorescence
emission
at
450
nm
and
568
nm.
determination
Cu(II)
was
performed
through
visual
analysis
color
change
intensity
ratio
(I450/I568)
peaks.
Orange
GSH-AuNCs
responded
fluorescence,
blue
CQDs
chemically
inert.
probes
changed
pink
purple
in
response
different
concentrations
Cu(II).
linear
range
for
0
120
µmol/L,
limit
(LOD)
0.65
µmol/L.
This
study
has
demonstrated
that
provided
good
selectivity
detecting
water
potential
practical
application.