A stimuli-responsive immunostimulant to activate chemo-immunotherapeutic effects by inducing DNA damage and STING activation
Journal of Colloid and Interface Science,
Год журнала:
2025,
Номер
688, С. 664 - 676
Опубликована: Фев. 26, 2025
Язык: Английский
Atovaquone-Coordinated Copper-Polyphenol Nanoplatform Orchestrates Dual Metabolic Interference for Synergistic Cuproptosis and Apoptosis
ACS Applied Materials & Interfaces,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 27, 2025
Cuproptosis,
a
copper-dependent
cell
death
mechanism,
is
hindered
by
tumor
microenvironment
(TME)-driven
resistance
including
glutathione
(GSH)-mediated
copper
detoxification
and
hypoxia-induced
metabolic
adaptation.
We
propose
"dual
interference"
strategy
to
amplify
cuproptosis
synergistically
targeting
iron–sulfur
(Fe–S)
cluster
proteins
suppressing
oxidative
phosphorylation
(OXPHOS).
A
TME-responsive
nanoplatform
(ACH
NPs)
was
constructed
based
on
copper-shikonin
coordination
network
(CuSK),
the
OXPHOS
inhibitor
atovaquone
(ATO),
hyaluronic
acid
(HA).
Upon
GSH/acid-triggered
release,
Cu+/Cu2+
ATO/SK
induced
irreversible
damage:
(1)
Copper
overload
induces
dihydrolipoamide
transacetylase
(DLAT)
aggregation
Fe–S
loss,
directly
disrupting
mitochondrial
complexes
I–III
functions;
(2)
ATO
further
suppresses
complex
III
activity,
reducing
oxygen
consumption
blocking
ATP
synthesis
exacerbate
crisis;
(3)
Concurrently,
Cu+-catalyzed
Fenton-like
reactions
synergize
with
SK-driven
stress
generate
•OH
radicals,
activating
Caspase-3-dependent
apoptosis.
In
vivo
experiments
verified
that
this
dual
interference
effectively
inhibited
growth
(86.8%
suppression).
These
findings
not
only
expand
theoretical
boundaries
of
but
also
establish
promising
paradigm
for
cancer
therapy
through
coordinated
metal
homeostasis
vulnerabilities.
Язык: Английский
Visible Light‐Triggered Precision SO2 Release from Polymeric Nanomedicine for Cancer Therapy
Small,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 7, 2025
Abstract
A
number
of
polymeric
sulfur
dioxide
(SO
2
)‐releasing
nanomedicines
have
demonstrated
promise
in
cancer
treatment
by
enabling
controlled
SO
release,
triggered
endogenous
(redox)
stimuli.
However,
the
heterogeneous
distribution
these
stimuli
across
different
organs
presents
a
significant
challenge
to
clinical
translation.
To
overcome
this
limitation,
developing
donors
that
respond
exogenous
triggers
offers
promising
strategy
for
therapeutic
advancement.
Herein,
an
stimuli‐responsive
is
presented
generating
from
series
amphiphilic
block
copolymers
(
BCPx
)
under
visible
light
irradiation
(427
nm)
biological
environment,
aiming
evaluate
their
potential
therapy.
The
coumarin‐based,
water‐soluble
polymers
form
well‐defined
nanostructures
BCPxNs
aqueous
media,
releasing
70–85%
theoretical
within
4
h.
Moreover,
exhibit
self‐reporting
behavior
upon
release.
In
vitro
cellular
assays
with
BCP2Ns
demonstrate
enhanced
antiproliferative
effect
cervical
carcinoma
HeLa
cells
nm),
IC
50
value
0.3
mg
mL
−1
.
Investigations
using
confocal
microscopy
and
flow
cytometry
confirm
‐induced
cell
death.
Overall,
underscores
light‐responsive
spatiotemporal
control
Язык: Английский