Abstract
The
maturation
of
dendritic
cells
(DCs)
represents
a
pivotal
determinant
in
tumor
immunotherapy
efficacy.
In
advanced
tumors,
the
immune‐suppressive
transforming
growth
factor‐beta
1
(TGF‐β1)
is
frequently
overexpressed
and
plays
central
role
immune
suppression.
Elevated
TGF‐β1
levels
significantly
impair
DCs
maturation,
leading
to
reduced
expression
major
histocompatibility
complex
(MHC)
molecules
inflammatory
cytokines,
consequently
diminishing
DCs‐mediated
T
cell
activation.
Here,
this
work
first
validates
presence
stable
G‐quadruplex
(G4)
structure
within
promoter
region.
To
minimize
off‐target
effects,
establishes
system
precisely
targeting
G4.
Through
CRISPR‐mediated
precise
G4
by
ligand
biotin‐labeled
pyridodicarboxamide
(Bio‐PDC),
demonstrates
its
functional
downregulating
expression.
By
combing
ZIF‐8
as
carrier
Bio‐PDC,
downregulation
enhanced
dual
pathway,
which
subsequently
facilitated
maturation.
These
results
highlight
key
regulatory
suggest
therapeutic
potential
synergistic
target
for
enhancing
efficacy
counteracting
evasion
mechanisms.
Acta Pharmaceutica Sinica B,
Год журнала:
2024,
Номер
14(9), С. 4087 - 4101
Опубликована: Июнь 3, 2024
Currently,
the
efficacy
of
albumin-bound
paclitaxel
(PTX@Alb)
is
still
limited
due
to
impaired
PTX@Alb
accumulation
in
tumors
partly
mediated
by
dense
collagen
distribution.
Meanwhile,
acquired
immune
resistance
always
occurs
enhanced
programmed
cell
death-ligand
1
(PD-L1)
expression
after
treatment,
which
then
leads
tolerance.
To
fill
these
gaps,
we
newly
revealed
that
tamoxifen
(TAM),
a
clinically
widely
used
adjuvant
therapy
for
breast
cancer
with
mitochondrial
metabolism
blockade
capacity,
could
also
be
as
novel
effective
PD-L1
and
TGF-
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.
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 17, 2025
Despite
the
promise
of
sonodynamic
therapy
(SDT)-mediated
immunotherapy,
anticancer
efficacy
current
sonosensitizers
is
greatly
limited
by
immunosuppressive
tumor
microenvironment
(TME)
and
their
inability
to
selectively
respond
it.
Herein,
oxygen
vacancy-rich
MnO2@hydroxyapatite
(Ca10(PO4)6(OH)2)
core-shell
nanospheres
(denoted
as
Ov-MO@CPO)
an
advanced
TME-responsive
sonosensitizer
for
immunotherapy
demonstrated.
The
Ov-MO@CPO
maintains
its
structural
integrity
under
neutral
conditions
but
dissolves
pH-sensitive
hydroxyapatite
shell
acidic
TME
release
active
MnO2
core,
which
reinvigorates
H2O2
consumption
hypoxia
alleviation
due
catalase-like
activity.
Furthermore,
introduced
vacancies
optimize
electronic
structure
Ov-MO@CPO,
with
states
near
Fermi
level
higher
d-band
center.
It
results
in
accelerated
electron-hole
pair
separation
lower
catalytic
energy
barriers
boost
ultrasound
(US)-initiated
ROS
production.
These
multimodal
synergistic
effects
effectively
reverse
microenvironment,
inhibiting
growth
metastasis
4T1
tumor-bearing
mice.
No
evident
toxic
are
observed
normal
mouse
tissues.
Additionally,
when
combined
immune
checkpoint
inhibitor,
Ov-MO@CPO-mediated
SDT
further
improves
effectiveness
immunotherapy.
This
work
affords
a
new
avenue
developing
TME-dependent
SDT-mediated
ONCOLOGIE,
Год журнала:
2024,
Номер
26(3), С. 487 - 491
Опубликована: Март 7, 2024
Abstract
Historically,
radiation
therapy
has
been
devoted
to
the
achievement
of
local
control
both
in
early
and
advanced
disease,
palliation
symptoms
(i.e.
pain),
treatment
cancer
complications
bone
fractures,
bleeding)
advanced/metastatic
cancer.
Recently,
discovery
role
as
a
trigger
activate
immune
system
led
an
increased
interest
among
insiders
regarding
interaction
between
host
reactions.
The
systemic
effects
are
widely
acknowledged
be
immunosuppressive
immunostimulant,
albeit
there
exists
considerable
uncertainty
doses/fraction
that
can
induce
them.
main
aim
this
brief
paper
is
describe
anti-tumor
responses
following
on
basis
selected
doses/fraction.
Journal of Nanobiotechnology,
Год журнала:
2024,
Номер
22(1)
Опубликована: Май 9, 2024
Abstract
Radiotherapy-induced
immune
activation
holds
great
promise
for
optimizing
cancer
treatment
efficacy.
Here,
we
describe
a
clinically
used
radiosensitizer
hafnium
oxide
(HfO
2
)
that
was
core
coated
with
MnO
shell
followed
by
glucose
oxidase
(GOx)
doping
nanoplatform
@MnO
@GOx,
HMG)
to
trigger
ferroptosis
adjuvant
effects
glutathione
depletion
and
reactive
oxygen
species
production.
This
cascade
potentiation
further
sensitized
radiotherapy
enhancing
DNA
damage
in
4T1
breast
tumor
cells.
The
combination
of
HMG
nanoparticles
effectively
activated
the
damaged
Mn
2+
-mediated
cGAS-STING
pathway
vitro
vivo.
process
had
significant
inhibitory
on
progression
initiating
an
anticancer
systemic
response
prevent
distant
recurrence
achieve
long-lasting
suppression
both
primary
tumors.
Furthermore,
as-prepared
“turned
on”
spectral
computed
tomography
(CT)/magnetic
resonance
dual-modality
imaging
signals,
demonstrated
favorable
contrast
enhancement
capabilities
under
GSH
microenvironment.
result
highlighted
potential
as
theranostic
achieving
molecular
guided
sensitization
induced
synergistic
immunotherapy.
