A pH-Responsive and Guanidinium-Rich Nanoadjuvant Efficiently Delivers STING Agonist for Cancer Immunotherapy
ACS Nano,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 11, 2025
As
natural
agonists
of
the
stimulator
interferon
genes
(STING),
cyclic
dinucleotides
(CDNs)
have
been
identified
as
promising
immunotherapies
that
trigger
a
potent
immune
response
against
tumors.
However,
low
stability,
rapid
clearance,
inadequate
cellular
uptake,
and
inefficient
cytosol
localization
heavily
hinder
therapeutic
efficacy
hydrophilic
negatively
charged
2′,
3′-cyclic-GMP-AMP
(cGAMP).
How
to
efficiently
deliver
cGAMP
into
endoplasmic
reticulum
(ER)
activate
STING
for
priming
remains
challenging.
Here,
we
report
pH-responsive
guanidinium-rich
nanoagonist
(nPGSA)
delivery
cGAMP.
Compared
with
free
cGAMP,
nPGSA
achieves
up
37.4-fold
enhancement
internalization.
The
pH-sensitive
guanidinium-functional
design
facilitates
quick
release
endosome
escape,
thus
enabling
precise
ER
targeting
33.9-fold
amplification
sensibilization.
Furthermore,
through
modulation
tumor-associated
macrophage
(TAM)
polarization,
elicits
antigen-specific
sustained
tumor
regression
in
melanoma-
neuroblastoma-bearing
mice.
Our
study
provides
strategy
it
offers
insights
function
modulating
microenvironment
cancer
immunotherapy.
Язык: Английский
NIR‐II Photoacoustic Imaging‐Guided Chemo‐Photothermal Therapy Using PA1094T Combined with Anti‐CD47 Antibody: Activating Pyroptosis against Orthotopic Glioblastoma
Advanced Healthcare Materials,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 30, 2024
Abstract
Treating
glioblastoma
(GBM)
with
single‐agent
chemotherapy
is
often
ineffective
due
to
inefficient
drug
delivery
and
the
immunosuppressive
tumor
microenvironment,
which
leads
resistance.
Strategies
that
activate
programmed
cell
death
mechanisms
repolarized
tumor‐associated
macrophages
toward
an
antitumoral
M1‐like
phenotype
can
help
reverse
microenvironment.
In
this
study,
a
novel
approach
using
NIR‐II
(1000–1700
nm)
photoacoustic
imaging
(PAI)‐guided
chemo‐photothermal
therapy
presented.
imaging,
its
superior
tissue
penetration
reduced
background
noise,
enables
precise
targeting.
A
targeted
nano
prodrug
developed
poly
(lactic
‐co
‐glycolic
acid)
nanoparticles
loaded
A1094
dye
temozolomide
(TMZ),
coupled
anti‐CD47
antibody.
This
system
employs
synergistic
activated
by
light,
inducing
apoptosis,
pyroptosis,
T‐cell
activation.
PAI
provides
rapid,
point‐of‐care
GBM
diagnosis,
highlighted
effective
targeting
of
PA1094T
nanoplatform.
recurrent
model,
combination
antibody
significantly
enhances
cancer
phagocytosis
effectively
remodels
resulting
in
better
therapeutic
outcomes
compared
conventional
therapies.
These
results
indicate
PAI‐guided
cocktail
promising
strategy
for
treating
GBM,
potentially
addressing
resistance
improving
treatment
efficacy
through
enhanced
immunomodulation.
Язык: Английский
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
Enhanced efficiency and selectivity in reactive oxygen species generation using thiazolo[5,4-d]thiazole-based supramolecular photosensitizers
Science China Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 21, 2025
Язык: Английский
Pyrazolo[1,5-a]pyrimidine-Based Type-I Photosensitizer as an Efficient Pyroptosis Inducer for Tumor Ablation
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 4, 2025
Pyroptosis
is
a
proinflammatory
and
lytic
programmed
cell
death
form,
which
can
promote
cytotoxic
T
lymphocyte
(CTL)
maturation
tumor
infiltration
through
the
release
of
damage-associated
molecular
patterns
(DAMPs).
Therefore,
induction
pyroptosis
by
small
molecules
promising
strategy
to
activate
antitumor
immunity.
In
this
work,
we
report
design
new
class
pyrazolo[1,5-a]pyrimidine-based
type-I
photosensitizers
(PSs)
as
efficient
inducers
for
cancer
photodynamic
therapy
(PDT).
Among
compounds,
ZS-3
exhibited
most
excellent
reactive
oxygen
species
(ROS)
generation
ability
phototoxicity
in
vitro.
It
was
found
that
induced
caspase-3/gasdermin
E
(GSDME)
pathway
under
light
irradiation,
characterized
bubble
formation
pattern
release.
Furthermore,
lipid
nanoparticles
significantly
inhibited
growth
evoked
immune
responses
vivo.
Язык: Английский
Homologous-Targeting Porous Type I/II Nanophotosensitizers for Efficient Delivery of STING Agonists and Enhanced Photodynamic Cancer Immunotherapy
ACS Applied Materials & Interfaces,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 8, 2025
Immunotherapy
as
a
transformative
cancer
treatment
modality
frequently
struggles
with
the
immunosuppressive
tumor
microenvironment,
which
hinders
effective
immune
responses.
In
this
report,
we
construct
biomimetic
cell
membrane-cloaked
porous
covalent
organic
framework
(COF)
nanophotosensitizers
(CMSCOFs)
to
synergistically
enhance
photodynamic
therapy
(PDT)
and
stimulate
interferon
genes
(STING)-mediated
immunotherapy.
CMSCOF
is
prepared
from
porphyrin
benzothiadiazole-based
units
cloaked
4T1
membranes
for
homologous
targeting.
The
structure
of
COF
enables
efficient
encapsulation
non-nucleotide
STING
agonist
SR717.
Upon
660
nm
light
irradiation,
CMSCOFs
trigger
both
type
I
II
effects
by
producing
superoxide
(O2•-)
singlet
oxygen
(1O2).
design
improves
stability
mimics
natural
cells
enhanced
blood
circulation,
accumulation,
homologous-targeting
tumors.
Inside
tissues,
unique
leads
immunogenic
death
(ICD)
upon
exposure
irradiation.
Furthermore,
encapsulated
SR717
released
after
cellular
internalization
activate
pathway
elicit
potent
antitumor
response.
This
synergistic
approach
effectively
reverses
enhances
cytotoxic
T
infiltration,
suppresses
primary
metastatic
tumors,
demonstrating
potential
promising
platform
Язык: Английский
Tumor hypoxia shapes natural killer cell anticancer activities
Journal of Molecular Medicine,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 30, 2025
Язык: Английский
Macrophage Vesicles‐Loaded NIR‐II AIEgens for Precise In Situ Fluorescence Imaging of Atherosclerosis
Small Methods,
Год журнала:
2025,
Номер
unknown
Опубликована: Июнь 2, 2025
Precise
diagnosis
of
atherosclerosis
(AS)
is
a
crucial
strategy
for
reducing
acute
cardiovascular
events.
Herein,
macrophage
membrane
(MM)-camouflaged
biomimetic
vesicle
loaded
with
near-infrared-II
(NIR-II)
aggregation-induced
emission
luminogens
(AIEgens)
(P4TT@MM)
proposed
to
achieve
localized
in
vivo
imaging
atherosclerosis.
The
AIEgens
characteristics
P4TT@MM
effectively
compensate
the
fluorescence
intensity
decrease
caused
by
intramolecular
torsional
charge
transfer
(TICT)
effect,
even
foam
cell-rich
lesions.
Benefiting
from
camouflage
MM
and
its
strong
affinity
atherosclerotic
plaques,
enables
precise
targeting
lesion
sites,
successfully
achieving
high-contrast
plaques
carotid
arteries
aortas
AS
mice
model.
Compared
free
P4TT,
NIR-II
increased
140%
152%
aortas,
respectively.
Moreover,
demonstrates
robust
biocompatibility
combined
significant
clinical
translation
potential.
This
study
may
present
promising
tool
AS.
Язык: Английский