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
Chemical Society Reviews,
Год журнала:
2023,
Номер
52(6), С. 2031 - 2081
Опубликована: Янв. 1, 2023
Bioactive
materials
are
a
special
class
of
biomaterials
that
can
react
in
vivo
to
induce
biological
response
or
regulate
functions,
thus
achieving
better
curative
effect
than
traditional
inert
biomaterials.
For
cancer
theranostics,
compared
with
organic
polymer
nanomaterials,
inorganic
nanomaterials
possess
unique
physical
and
chemical
properties,
have
stronger
mechanical
stability
on
the
basis
maintaining
certain
bioactivity,
easy
be
compounded
various
carriers
(polymer
carriers,
etc.),
so
as
achieve
specific
antitumor
efficacy.
After
entering
nanoscale,
due
nano-size
effect,
high
surface
area
nanostructures,
exhibit
effects,
which
significantly
influence
interaction
organisms.
Therefore,
research
applications
bioactive
theranostics
attracted
wide
attention.
In
this
review,
we
mainly
summarize
recent
progress
also
introduce
definition,
synthesis
modification
strategies
nanomaterials.
Thereafter,
tumor
imaging
therapy,
including
microenvironment
(TME)
regulation,
catalytic
gas
regulatory
cell
death
immunotherapy,
discussed.
Finally,
biosafety
challenges
mentioned,
their
future
development
opportunities
prospected.
This
review
highlights
bioapplication
Journal of the American Chemical Society,
Год журнала:
2023,
Номер
145(11), С. 6007 - 6023
Опубликована: Март 7, 2023
Pyroptosis
refers
to
the
process
of
gasdermin-mediated
lytic
programmed
cell
death
(PCD)
characterized
by
release
pro-inflammatory
cytokines.
Our
knowledge
pyroptosis
has
expanded
beyond
cellular
level
and
now
includes
extracellular
responses.
In
recent
years,
attracted
considerable
attention
due
its
potential
induce
host
immunity.
For
instance,
at
2022
International
Medicinal
Chemistry
Natural
Active
Ligand
Metal-Based
Drugs
(MCNALMD)
conference,
numerous
researchers
demonstrated
an
interest
in
photon-controlled
activation
("PhotoPyro"),
emerging
pyroptosis-engineered
approach
for
activating
systemic
immunity
via
photoirradiation.
Given
this
enthusiasm,
we
share
Perspective
our
views
on
area
expound
how
why
"PhotoPyro"
could
trigger
antitumor
(i.e.,
turning
so-called
"cold"
tumors
"hot").
doing
so,
have
tried
highlight
cutting-edge
breakthroughs
PhotoPyro
while
suggesting
areas
future
contributions.
By
providing
insights
into
current
state
art
serving
as
a
resource
individuals
interested
working
area,
it
is
hoped
that
will
set
stage
evolve
broadly
applicable
cancer
treatment
strategy.
Chemical Reviews,
Год журнала:
2023,
Номер
123(16), С. 10135 - 10155
Опубликована: Авг. 3, 2023
Over
the
last
few
decades,
various
forms
of
regulated
cell
death
(RCD)
have
been
discovered
and
were
found
to
improve
cancer
treatment.
Although
there
are
several
reviews
on
RCD
induced
by
photodynamic
therapy
(PDT),
a
comprehensive
summary
covering
metal-based
photosensitizers
(PSs)
as
inducers
has
not
yet
presented.
In
this
review,
we
systematically
summarize
works
PSs
that
induce
different
types
RCD,
including
ferroptosis,
immunogenic
(ICD),
pyroptosis.
The
characteristics
mechanisms
each
explained.
At
end
section,
reported
commonalities
between
inducing
same
is
emphasized,
future
perspectives
novel
discussed
at
review.
Considering
essential
roles
in
therapy,
hope
review
will
provide
stage
for
advances
inducers.
Journal of the American Chemical Society,
Год журнала:
2023,
Номер
145(30), С. 16658 - 16668
Опубликована: Июль 24, 2023
Pyroptosis
is
an
inflammatory
form
of
programmed
cell
death
that
holds
great
promise
in
cancer
therapy.
However,
autophagy
as
the
crucial
pyroptosis
checkpoint
and
self-protective
mechanism
cells
significantly
weakens
therapeutic
efficiency.
Here,
a
bioorthogonal
nanoregulator
constructed
to
induce
disrupt
checkpoint,
enabling
high-efficiency
The
allows
situ
synthesis
accumulation
photosensitizer
PpIX
mitochondria
directly
produce
mitochondrial
ROS,
thus
triggering
pyroptosis.
Meanwhile,
generated
inhibitor
via
palladium-catalyzed
chemistry
can
boost
efficacy.
With
biomimetic
membrane
coating,
this
platform
for
modulating
presents
specificity
poses
no
harm
normal
tissue,
resulting
highly
efficient
safe
antitumor
treatment.
To
our
knowledge,
first
report
on
disrupting
intrinsic
protective
tumor
This
work
highlights
plays
key
regulative
role
therapy,
which
would
motivate
future
design
regimens.
Advanced Materials,
Год журнала:
2024,
Номер
36(21)
Опубликована: Фев. 14, 2024
Activation
of
the
cyclic
GMP-AMP
synthase-stimulator
interferon
genes
(cGAS-STING)
pathway
has
emerged
as
an
efficient
strategy
to
improve
therapeutic
outcomes
immunotherapy.
However,
"constantly
active"
mode
current
STING
agonist
delivery
strategies
typically
leads
off-target
toxicity
and
hyperimmunity.
To
address
this
critical
issue,
herein
a
metal-organic
frameworks-based
nanoagonist
(DZ@A7)
featuring
tumor-specific
near-infrared
(NIR)
light-enhanced
decomposition
is
constructed
for
precisely
localized
activation
photodynamic-metalloimmunotherapy.
The
engineered
enabled
generation
mitochondria-targeted
reactive
oxygen
species
under
NIR
irradiation
specifically
release
mitochondrial
DNA
(mtDNA)
inhibit
repair
nuclear
via
hypoxia-responsive
drugs.
Oxidized
tumor
mtDNA
serves
endogenous
danger-associated
molecular
pattern
that
activates
cGAS-STING
pathway.
Concurrently,
NIR-accelerated
zinc
ions
overloading
in
cancer
cells
further
enhance
cGAS
enzymatic
activity
through
metalloimmune
effects.
By
combining
synergistically
enhanced
triggered
by
irradiation,
facilitated
maturation
dendritic
infiltration
cytotoxic
T
lymphocytes
primary
eradication,
which
also
established
long-term
anti-tumor
immunity
suppress
metastasis.
Therefore,
developed
NIR-triggered,
agonist-free,
tandem-amplified
pathway,
thereby
offering
distinct
paradigm
Cell Communication and Signaling,
Год журнала:
2024,
Номер
22(1)
Опубликована: Янв. 9, 2024
Abstract
Background
Intracellular
DNA-sensing
pathway
cGAS-STING,
inflammasomes
and
pyroptosis
act
as
critical
natural
immune
signaling
axes
for
microbial
infection,
chronic
inflammation,
cancer
progression
organ
degeneration,
but
the
mechanism
regulation
of
crosstalk
network
remain
unclear.
Main
body
abstract
Cellular
stress
disrupts
mitochondrial
homeostasis,
facilitates
opening
permeability
transition
pore
leakage
DNA
to
cell
membrane,
triggers
inflammatory
responses
by
activating
cGAS-STING
signaling,
subsequently
induces
activation
onset
pyroptosis.
Meanwhile,
inflammasome-associated
protein
caspase-1,
Gasdermin
D,
CARD
domain
ASC
potassium
channel
are
involved
in
regulating
pathway.
Importantly,
this
has
a
cascade
amplification
effect
that
exacerbates
immuno-inflammatory
response,
worsening
pathological
process
autoimmune
diseases.
Given
importance
innate
immunity,
it
is
emerging
new
avenue
explore
mechanisms
multiple
disease
pathogenesis.
Therefore,
efforts
define
strategies
selectively
modulate
different
settings
have
been
or
ongoing.
In
review,
we
will
describe
how
mechanistic
understanding
driving
possible
therapeutics
targeting
network,
focusing
on
interacting
regulatory
proteins,
pathways,
hub
between
inflammasomes,
Short
conclusion
This
review
aims
provide
insight
into
roles
pyroptosis,
highlight
some
promising
directions
future
research
intervention.
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
67(5), С. 3843 - 3859
Опубликована: Март 5, 2024
To
develop
a
potential
theranostic
metal
agent
to
reverse
the
resistance
of
cancer
cells
cisplatin
and
effectively
inhibit
tumor
growth
metastasis,
we
proposed
design
cyclometalated
iridium
(Ir)
complex
based
on
properties
environment
(TME).
end,
designed
synthesized
series
Ir(III)
2-hydroxy-1-naphthaldehyde
thiosemicarbazone
complexes
by
modifying
hydrogen
atom(s)
N-3
position
compounds
structure
dimers
then
investigated
their
structure–activity
structure–fluorescence
relationships
obtain
an
(Ir5)
with
remarkable
fluorescence
cytotoxicity
cells.
Ir5
not
only
possesses
mitochondria-targeted
but
also
overcomes
inhibits
metastasis
in
vivo.
Besides,
confirmed
anticancer
mechanisms
acting
different
components
TME:
directly
killing
liver
inducing
necroptosis
activating
necroptosis-related
immune
response.
