Recent
research
has
demonstrated
that
activating
the
cGAS-STING
pathway
can
enhance
interferon
production
and
activation
of
T
cells.
A
manganese
complex,
called
TPA-Mn,
was
developed
in
this
context.
The
reactive
oxygen
species
(ROS)-sensitive
nanoparticles
(NPMn)
loaded
with
TPA-Mn
are
developed.
NPMn
activates
via
cGAS
(i.e.,
1.6-fold
enhancement
P-STING),
which
turn
increases
secretion
pro-inflammatory
cytokines
(e.g.,
TNF-α,
IL-6,
IL-2).
This
promotes
dendritic
cell
maturation,
enhances
infiltration
cytotoxic
lymphocytes,
reduces
percentage
immunosuppressive
regulatory
In
addition,
it
is
crucial
to
emphasize
cisplatin-induced
DNA
damage
potentially
trigger
pathway.
NPMn,
combination
low-dose
NPPt,
a
carrier
Cis(IV)
prodrug
capable
causing
damage,
augments
significantly
tumor
immune
microenvironment
(TIME).
Furthermore,
combined
anti-PD-1
antibody,
NPPt+NPMn
shows
synergistic
efficacy
both
ovarian
cancer
peritoneal
metastases
recurrence
models.
It
not
only
effectively
eliminates
tumors
but
also
induces
strong
memory
response,
providing
promising
strategy
for
clinical
management
cancer.
work
offers
design
manganese-based
immunotherapy.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(37)
Опубликована: Май 22, 2024
Though
platinum
(Pt)-based
complexes
have
been
recently
exploited
as
immunogenic
cell
death
(ICD)
inducers
for
activating
immunotherapy,
the
effective
activation
of
sufficient
immune
responses
with
minimal
side
effects
in
deep-seated
tumors
remains
a
formidable
challenge.
Herein,
we
propose
first
example
near-infrared
(NIR)
light-activated
and
lysosomal
targeted
Pt(II)
metallacycle
(1)
supramolecular
ICD
inducer.
1
synergistically
potentiates
immunomodulatory
response
via
multiple-regulated
approaches,
involving
NIR
light
excitation,
boosted
reactive
oxygen
species
(ROS)
generation,
good
selectivity
between
normal
tumor
cells,
enhanced
penetration/retention
capabilities.
Specifically,
has
excellent
depth-activated
ROS
production
(~7
mm),
accompanied
by
strong
anti-diffusion
anti-ROS
quenching
ability.
In
vitro
experiments
demonstrate
that
exhibits
significant
cellular
uptake
generation
cells
well
respective
multicellular
spheroids.
Based
on
these
advantages,
induces
more
efficient
an
ultralow
dose
(i.e.,
5
μM)
compared
clinical
inducer-oxaliplatin
(300
μM).
vivo,
vaccination
further
serves
potent
inducer
through
eliciting
CD8
Advanced Healthcare Materials,
Год журнала:
2024,
Номер
13(20)
Опубликована: Март 26, 2024
The
emerging
cell
death
modality
of
ferroptosis
has
garnered
increasing
attention
for
antitumor
treatment
but
still
suffers
from
low
therapeutic
efficacy.
A
metal-organic
frameworks
(MOFs)-based
magnetic
nanozyme
(PZFH)
comprising
porphyrin-based
Zr-MOF
(PCN)
on
zinc
ferrite
(ZF)
nanoparticles
modified
with
hyaluronic
acid,
delivering
excellent
magnetophotonic
response
efficient
ferroptosis,
is
reported
here.
PZFH
shows
multienzyme-like
cascade
activity
encompassing
a
photon-triggered
oxidase-like
catalysis
to
generate
O
Advanced Materials,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 29, 2024
Given
the
crucial
role
of
abnormal
homeostasis
in
tumor
cells
for
maintaining
their
growth,
it
may
be
more
efficient
with
less
effort
to
develop
anti-tumor
strategies
that
target
multiple
combined
mechanisms
by
disrupting
intracellular
homeostasis.
Here,
a
copper-based
nanoinducer
(CGBH
NNs)
enzyme-like
activities
is
designed
and
constructed
induce
disulfidptosis-enhanced
pyroptosis
through
effective
immunotherapy.
Within
microenvironment
(TME),
CGBH
NNs
can
disrupt
glucose
inhibit
NADPH
production,
leading
accumulation
cystine,
which
further
blocked
substrate
key
enzyme
synthesizing
glutathione.
Subsequently,
cascade
catalytic
reactions
involving
(glutathione
peroxidase-like,
oxidase
peroxidase-like
activities),
produce
massive
reactive
oxygen
species
(ROS)
redox
homeostasis,
resulting
pyroptosis.
The
undergoing
immunogenic
release
various
cytosolic
contents
inflammatory
factors,
eliciting
robust
immune
responses
facilitating
cell
infiltration,
reprogramming
immunosuppressive
TME.
After
combination
checkpoint
blockade
therapy,
effectively
suppress
growth
prolong
survival
time
tumor-bearing
mice.
This
work
presents
novel
paradigm
trigger
destroying
ACS Nano,
Год журнала:
2024,
Номер
18(43), С. 30053 - 30068
Опубликована: Окт. 16, 2024
The
endoplasmic
reticulum
(ER)
and
mitochondria
are
essential
organelles
that
play
crucial
roles
in
maintaining
cellular
homeostasis.
simultaneous
induction
of
ER
stress
mitochondrial
dysfunction
represents
a
promising
yet
challenging
strategy
for
cancer
treatment.
Herein,
hollow
calcium–copper
bimetallic
nanoplatform
is
developed
as
cascade
amplifier
to
reinforce
breast
For
this
purpose,
we
report
facile
method
preparing
CaCO3
(HCC)
nanoparticles
by
regulating
the
dissolution–recrystallization
process
amorphous
CaCO3,
D@HCC-CuTH
meticulously
fabricated
sequentially
coating
disulfiram-loaded
HCC
with
copper
coordination
polymer
hyaluronan.
In
tumor
cells,
dithiocarbamate–copper
complex
generated
situ
liberated
disulfiram
Cu2+
inhibits
ubiquitin–proteasome
system,
causing
irreversible
intracellular
Ca2+
redistribution.
Meanwhile,
induces
via
triggering
self-amplifying
loop
burst,
reactive
oxygen
species
augment.
Additionally,
dihydrolipoamide
S-acetyltransferase
oligomerization
mitochondria,
further
exacerbating
damage
cuproptosis.
Collectively,
amplification
synergistically
induce
cuproptosis–paraptosis–apoptosis
trimodal
cell
death
pathway,
which
demonstrates
significant
efficacy
suppressing
growth.
This
study
presents
paradigm
synchronously
inducing
subcellular
organelle
disorders
boost
multimodal
therapy.
Journal of Medicinal Chemistry,
Год журнала:
2023,
Номер
66(18), С. 13072 - 13085
Опубликована: Сен. 13, 2023
To
develop
next-generation
metal
drugs
with
high
efficiency
and
low
toxicity
for
targeting
inhibition
of
gastric
tumor
growth
metastasis,
we
not
only
optimized
a
series
ruthenium
(Ru,
III)
2-hydroxy-1-naphthaldehyde
thiosemicarbazone
complexes
to
obtain
Ru(III)
complex
(4b)
remarkable
cytotoxicity
in
vitro
but
also
constructed
4b-decitabine
(DCT)/liposome
(Lip)
delivery
system
(4b-DCT-Lip).
The
vivo
results
showed
that
4b-DCT-Lip
had
stronger
capacity
inhibit
metastasis
than
4b-DCT
addressed
the
co-delivery
problems
improved
their
ability.
Furthermore,
confirmed
mechanism
4b-DCT/4b-DCT-Lip
inhibiting
tumor.
DCT-upregulated
gasdermin
E
(GSDME)
was
cleaved
by
4b-activated
caspase-3
afford
GSDME-N
terminal
then
aggregated
form
nonselective
pores
on
cell
membrane
tumor,
thereby
inducing
pyroptosis
pyroptosis-induced
immune
response.
Journal of Medicinal Chemistry,
Год журнала:
2023,
Номер
67(1), С. 691 - 708
Опубликована: Дек. 23, 2023
A
second-generation
series
of
biscyclometalated
2-(5-aryl-thienyl)-benzimidazole
and
-benzothiazole
Ir(III)
dppz
complexes
[Ir(C^N)2(dppz)]+,
Ir1–Ir4,
were
rationally
designed
synthesized,
where
the
aryl
group
attached
to
thienyl
ring
was
p-CF3C6H4
or
p-Me2NC6H4.
These
new
assessed
as
photosensitizers
explore
structure–activity
correlations
for
their
potential
use
in
biocompatible
anticancer
photodynamic
therapy.
When
irradiated
with
blue
light,
exhibited
high
selective
potency
across
several
cancer
cell
lines
predisposed
therapy;
benzothiazole
derivatives
(Ir1
Ir2)
best
performers,
Ir2
being
also
activatable
green
red
light.
Notably,
when
irradiated,
induced
leakage
lysosomal
content
into
cytoplasm
HeLa
cells
oncosis-like
death.
The
capability
Ir
photoinduce
death
3D
spheroids
has
been
demonstrated.
investigated
can
catalytically
photo-oxidate
NADH
photogenerate
1O2
and/or
•OH
cell-free
media.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(49)
Опубликована: Авг. 24, 2024
Abstract
The
integration
of
pyroptosis
and
ferroptosis
hybrid
cell
death
induction
to
augment
immune
activation
represents
a
promising
avenue
for
anti‐tumor
treatment,
but
there
is
lack
research.
Herein,
we
developed
two
iridium
(III)‐triphenylamine
photosensitizers,
IrC
IrF
,
with
the
capacity
disrupt
redox
balance
induce
photo‐driven
cascade
damage
DNA
Kelch‐like
ECH‐associated
protein
1
(KEAP1).
absent
in
melanoma
2
(AIM2)‐related
cytoplasmic
nucleic
acid‐sensing
pathway,
triggered
by
damaged
DNA,
leads
gasdermin
D
(GSDMD)‐mediated
pyroptosis.
Simultaneously,
iron
homeostasis,
regulated
KEAP1/nuclear
factor
erythroid
2‐related
(NRF2)/heme
oxygenase
(HO‐1)
serves
as
pivotal
bridge,
facilitating
not
only
E
(GSDME)‐mediated
non‐canonical
pyroptosis,
also
synergy
glutathione
peroxidase
4
(GPX4)
depletion.
collaborative
action
generates
synergistic
effect
that
elicits
immunogenic
death,
stimulates
robust
response
effectively
inhibits
tumor
growth
vivo.
Our
work
introduces
first
metal‐based
small
molecule
dual‐inducers
potent
cancer
immunotherapy,
highlights
significance
homeostasis
vital
hub
connecting
effects
ferroptosis.