Radiotherapy
is
crucial
in
local
cancer
management
and
needs
advancements.
Tumor
cells
elevate
intracellular
copper
levels
to
promote
growth
resist
radiation;
thus,
targeted
delivery
mitochondria
could
enhance
radiotherapy
by
inducing
cuproptosis
tumor
cells.
In
this
study,
we
engineered
a
multifunctional
nanoliposome
complex,
termed
Lipo-Ele@CuO2,
which
encapsulates
both
peroxide
(CuO2)
the
chelator
elesclomol,
can
Cu
ions
mitochondria.
The
Lipo-Ele@CuO2
complex
induces
mitochondria-mediated
synergistically
enhances
efficacy
of
radiotherapy.
CuO2
acts
as
donor
exhibits
inherent
sensitivity
acidic
environments.
Additionally,
it
depletes
glutathione,
thereby
sensitizing
cuproptosis.
Leveraging
its
pH-responsive
properties
microenvironment,
facilitate
controlled
release
efficiently
delivering
at
sites.
combined
vitro
vivo
studies
demonstrate
that
Lipo-Ele@CuO2-based
therapy
significantly
improves
antitumor
excellent
safety
profiles,
effectively
boosting
effectiveness
Furthermore,
metabolomic
transcriptomic
analyses
reveal
combination
precipitates
significant
alterations
energy
metabolism,
notably
repressing
genes
related
iron-sulfur
cluster
assembly
glycolysis,
confirming
induction
This
therapeutic
strategy
provides
viable
approach
for
addressing
clinical
resistance
demonstrates
translational
potential.
Clinical and Experimental Medicine,
Год журнала:
2025,
Номер
25(1)
Опубликована: Янв. 3, 2025
Donafenib
is
an
improved
version
of
sorafenib
in
which
deuterium
substituted
into
the
drug's
chemical
structure,
enhancing
its
stability
and
antitumor
activity.
exhibits
enhanced
activity
better
tolerance
than
preclinical
clinical
studies.
However,
specific
mechanism
effect
on
hepatocellular
carcinoma
has
not
been
reported.
Iron
deposition
a
cell
death
pattern
caused
by
disturbances
iron
metabolism.
Apoptosis
form
programmed
death.
They
may
interact
with
each
other
during
This
study
mainly
explores
potential
donafenib
activating
p53
signaling
pathway,
inducing
deposition,
apoptosis
carcinoma.
Hepa1-6
Huh7
cells
were
treated
various
concentrations
donafenib.
Scratch
healing
pore
migration
tests
conducted.
Analyze
through
flow
cytometry
TUNEL
fluorescence
labeling.
RNA
sequencing
was
conducted
both
untreated
donafenib-treated
cells.
The
key
proteins
involved
ferroptosis
(SLC7A11,
GPX4)
(caspase3,
caspase8,
Bax,
Bcl-2,
p53)
then
evaluated
using
immunoblotting
immunohistochemical
staining.
Reactive
oxygen
species
(ROS)
levels
cancer
measured.
treatment
resulted
dose-dependent
decrease
proliferation,
migration,
invasion
capabilities
There
increase
rates
ROS
accumulation,
reduction
tumor
volume.
underwent
significant
changes.
activates
induce
ferroptosis,
enhance
apoptosis,
suggesting
as
effective
therapeutic
agent
for
HCC.
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(3), С. 1193 - 1193
Опубликована: Янв. 30, 2025
The
structural
and
functional
integrity
of
the
retinal
pigment
epithelium
(RPE)
plays
a
key
role
in
normal
functioning
visual
system.
RPE
cells
are
characterized
by
an
efficient
system
photoreceptor
outer
segment
phagocytosis,
high
metabolic
activity,
risk
oxidative
damage.
dysfunction
is
common
pathological
feature
various
diseases.
Dysregulation
cell
proteostasis
redox
homeostasis
accompanied
increased
reactive
oxygen
species
generation
during
impairment
lysosomal
mitochondrial
failure,
accumulation
waste
lipidic
protein
aggregates.
They
inducers
can
trigger
specific
pathways
death.
Autophagy
serves
as
important
mechanism
endogenous
defense
system,
controlling
survival
under
conditions
cellular
responses
stress
through
degradation
intracellular
components.
Impairment
autophagy
process
itself
result
In
this
review,
we
summarize
classical
types
stress-induced
with
emphasis
on
mediated
molecular
chaperones.
Heat
shock
proteins,
which
represent
hubs
connecting
life
supporting
cells,
play
special
these
mechanisms.
Regulation
stress-counteracting
essential
strategy
for
protecting
against
damage
when
preventing
degenerative
disease
progression.
Radiotherapy
is
crucial
in
local
cancer
management
and
needs
advancements.
Tumor
cells
elevate
intracellular
copper
levels
to
promote
growth
resist
radiation;
thus,
targeted
delivery
mitochondria
could
enhance
radiotherapy
by
inducing
cuproptosis
tumor
cells.
In
this
study,
we
engineered
a
multifunctional
nanoliposome
complex,
termed
Lipo-Ele@CuO2,
which
encapsulates
both
peroxide
(CuO2)
the
chelator
elesclomol,
can
Cu
ions
mitochondria.
The
Lipo-Ele@CuO2
complex
induces
mitochondria-mediated
synergistically
enhances
efficacy
of
radiotherapy.
CuO2
acts
as
donor
exhibits
inherent
sensitivity
acidic
environments.
Additionally,
it
depletes
glutathione,
thereby
sensitizing
cuproptosis.
Leveraging
its
pH-responsive
properties
microenvironment,
facilitate
controlled
release
efficiently
delivering
at
sites.
combined
vitro
vivo
studies
demonstrate
that
Lipo-Ele@CuO2-based
therapy
significantly
improves
antitumor
excellent
safety
profiles,
effectively
boosting
effectiveness
Furthermore,
metabolomic
transcriptomic
analyses
reveal
combination
precipitates
significant
alterations
energy
metabolism,
notably
repressing
genes
related
iron-sulfur
cluster
assembly
glycolysis,
confirming
induction
This
therapeutic
strategy
provides
viable
approach
for
addressing
clinical
resistance
demonstrates
translational
potential.
