Advanced Materials,
Journal Year:
2023,
Volume and Issue:
35(42)
Published: July 18, 2023
Despite
recent
advancements
in
cancer
immunotherapy,
challenges
have
yet
to
be
surmounted
achieve
two
major
goals
of
magnifying
antitumor
immunity
and
remodeling
the
immunosuppressive
tumor
microenvironment.
Here,
a
nanosystem
(ODM-R)
that
integrates
oxygen-deficient
molybdenum
oxide
(ODM)
nanosonosensitizers
R7
peptides
with
metabolism
regulation
effects
is
designed
fabricated
for
synergistic
sonodynamic-immunometabolic
therapy
spinal-metastasized
tumors.
The
ODM
generates
reactive
oxygen
species
upon
ultrasound
irradiation
implement
sonodynamic
(SDT),
inducing
cell
apoptosis
immunogenic
death.
attached
on
markedly
inhibits
uptake
glucose
excretion
lactic
acid
cells
by
perturbing
glycolysis
process.
combination
SDT
obstruction
ODM-R
guarantees
satisfactory
efficacy
synergizing
PD-L1
antibody
eradicate
tumors,
achieving
concurrent
sonodynamic-triggered
immune
activation
microenvironment
remodeling.
This
work
provides
proof-of-concept
boosting
immunotherapy
metabolic
regulation.
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: March 1, 2023
The
TP53
tumor
suppressor
is
the
most
frequently
altered
gene
in
human
cancers,
and
has
been
a
major
focus
of
oncology
research.
p53
protein
transcription
factor
that
can
activate
expression
multiple
target
genes
plays
critical
roles
regulating
cell
cycle,
apoptosis,
genomic
stability,
widely
regarded
as
"guardian
genome".
Accumulating
evidence
shown
also
regulates
metabolism,
ferroptosis,
microenvironment,
autophagy
so
on,
all
which
contribute
to
suppression.
Mutations
not
only
impair
its
function,
but
confer
oncogenic
properties
mutants.
Since
mutated
inactivated
malignant
tumors,
it
very
attractive
for
developing
new
anti-cancer
drugs.
However,
until
recently,
was
considered
an
"undruggable"
little
progress
made
with
p53-targeted
therapies.
Here,
we
provide
systematic
review
diverse
molecular
mechanisms
signaling
pathway
how
mutations
impact
progression.
We
discuss
key
structural
features
inactivation
by
mutations.
In
addition,
efforts
have
therapies,
challenges
encountered
clinical
development.
Advanced Materials,
Journal Year:
2023,
Volume and Issue:
35(33)
Published: March 7, 2023
Abstract
Immunotherapy
has
made
remarkable
strides
in
cancer
therapy
over
the
past
decade.
However,
such
emerging
still
suffers
from
low
response
rates
and
immune‐related
adverse
events.
Various
strategies
have
been
developed
to
overcome
these
serious
challenges.
Therein,
sonodynamic
(SDT),
as
a
non‐invasive
treatment,
received
ever‐increasing
attention
especially
treatment
of
deep‐seated
tumors.
Significantly,
SDT
can
effectively
induce
immunogenic
cell
death
trigger
systemic
anti‐tumor
immune
response,
termed
immunotherapy.
The
rapid
development
nanotechnology
revolutionized
effects
with
robust
induction.
As
result,
more
innovative
nanosonosensitizers
synergistic
modalities
are
established
superior
efficacy
safe
profile.
In
this
review,
recent
advances
immunotherapy
summarized
particular
emphasis
on
how
be
explored
harness
for
amplifying
response.
Moreover,
current
challenges
field
prospects
its
clinical
translation
also
presented.
It
is
anticipated
that
review
provide
rational
guidance
facilitate
nanomaterials‐assisted
immunotherapy,
helping
pave
way
next‐generation
eventually
achieve
durable
patients.
Advanced Materials,
Journal Year:
2023,
Volume and Issue:
35(51)
Published: June 1, 2023
Sonodynamic
therapy
(SDT)
is
a
promising
non-invasive
therapeutic
modality
to
treat
deep-seated
tumors
owing
the
good
tissue
penetration
ability
and
spatiotemporal
controllability
of
ultrasound
(US);
however,
low
sonodynamic
activity
potential
side
effects
greatly
limit
its
clinical
translation.
Cancer
immunotherapy
that
leverages
immune
system
fight
against
cancer
has
great
synergize
with
SDT
for
treatment
high
efficiency
safety.
In
this
review,
convergence
exert
their
merits
break
through
limitations
combination
sono-immunotherapy
are
discussed.
The
focus
on
development
construction
organic
materials
immunotherapeutic
efficiency.
These
not
only
induce
immunogenic
cell
death
improve
tumor
immunogenicity
via
but
also
activate
antitumor
immunity
immuno-oncology
drug-mediated
pathway
modulation.
various
drugs
sonosensitizers
categorized
discussed
along
prospects
challenges
Advanced Materials,
Journal Year:
2022,
Volume and Issue:
35(6)
Published: Nov. 25, 2022
Abstract
Checkpoint
immunotherapy
holds
great
potential
to
treat
malignancies
via
blocking
the
immunosuppressive
signaling
pathways,
which
however
suffers
from
inefficiency
and
off‐target
adverse
effects.
Herein,
checkpoint
nano‐proteolysis
targeting
chimeras
(nano‐PROTACs)
in
combination
with
photodynamic
tumor
regression
protein
degradation
block
pathways
for
activatable
cancer
photo‐immunotherapy
are
reported.
These
nano‐PROTACs
composed
of
a
photosensitizer
(protoporphyrin
IX,
PpIX)
an
Src
homology
2
domain‐containing
phosphatase
(SHP2)‐targeting
PROTAC
peptide
(aPRO)
caspase
3‐cleavable
segment.
aPRO
is
activated
by
increased
expression
3
cells
after
phototherapeutic
treatment
induces
targeted
SHP2
ubiquitin‐proteasome
system.
The
persistent
depletion
blocks
(CD47/SIRPα
PD‐1/PD‐L1),
thus
reinvigorating
antitumor
macrophages
T
cells.
Such
strategy
synergizes
immunogenic
phototherapy
boost
immune
response.
Thus,
this
study
represents
generalized
platform
modulate
immune‐related
improved
anticancer
therapy.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(9)
Published: Jan. 2, 2023
Oxygen-deficient
molybdenum
oxide
(MoOX
)
nanomaterials
are
prepared
as
novel
nanosensitizers
and
TME-stimulants
for
ultrasound
(US)-enhanced
cancer
metalloimmunotherapy.
After
PEGylation,
MoOX
-PEG
exhibits
efficient
capability
US-triggered
reactive
oxygen
species
(ROS)
generation
glutathione
(GSH)
depletion.
Under
US
irradiation,
generates
a
massive
amount
of
ROS
to
induce
cell
damage
immunogenic
death
(ICD),
which
can
effectively
suppress
tumor
growth.
More
importantly,
itself
further
stimulates
the
maturation
dendritic
cells
(DCs)
triggeres
activation
cGAS-STING
pathway
enhance
immunological
effect.
Due
robust
ICD
induced
by
SDT
DC
stimulated
-PEG,
combination
treatment
-triggered
aCTLA-4
amplifies
antitumor
therapy,
inhibits
metastases,
elicits
immune
responses
defeat
abscopal
tumors.
Advanced Materials,
Journal Year:
2023,
Volume and Issue:
35(18)
Published: Feb. 21, 2023
Tumor
immunotherapy
based
on
immune
checkpoint
blockade
(ICB)
still
suffers
from
low
host
response
rate
and
non-specific
distribution
of
inhibitors,
greatly
compromising
the
therapeutic
efficiency.
Herein,
cellular
membrane
stably
expressing
matrix
metallopeptidase
2
(MMP2)-activated
PD-L1
blockades
is
engineered
to
coat
ultrasmall
barium
titanate
(BTO)
nanoparticle
for
overcoming
immunosuppressive
microenvironment
tumors.
The
resulting
M@BTO
NPs
can
significantly
promote
BTO's
tumor
accumulation,
while
masking
domains
antibodies
are
cleaved
when
exposure
MMP2
highly
expressed
in
tumor.
With
ultrasound
(US)
irradiation,
simultaneously
generate
reactive
oxygen
species
(ROS)
O2
BTO
mediated
piezocatalysis
water
splitting,
promoting
intratumoral
infiltration
cytotoxic
T
lymphocytes
(CTLs)
improving
therapy
tumor,
effective
growth
inhibition
lung
metastasis
suppression
a
melanoma
mouse
model.
This
nanoplatform
combines
MMP2-activated
genetic
editing
cell
with
US
responsive
both
stimulation
specific
inhibition,
providing
safe
robust
strategy
enhancing
against
Advanced Science,
Journal Year:
2023,
Volume and Issue:
10(10)
Published: Feb. 2, 2023
Immunotherapy
is
an
attractive
treatment
strategy
for
cancer,
while
its
efficiency
and
safety
need
to
be
improved.
A
dual-cascade
activatable
nanopotentiator
sonodynamic
therapy
(SDT)
chemodynamic
(CDT)-cooperated
immunotherapy
of
deep
tumors
via
reshaping
adenosine
metabolism
herein
reported.
This
(NPMCA)
constructed
through
crosslinking
deaminase
(ADA)
with
chlorin
e6
(Ce6)-conjugated
manganese
dioxide
(MnO2)
nanoparticles
a
reactive
oxygen
species
(ROS)-cleavable
linker.
In
the
tumor
microenvironment
ultrasound
(US)
irradiation,
NPMCA
mediates
CDT
SDT
concurrently
in
covered
2-cm
tissues
produce
abundant
ROS,
which
results
scissoring
ROS-cleavable
linkers
activate
ADA
within
NCMCA
block
metabolism.
Moreover,
immunogenic
cell
death
(ICD)
dying
cells
upregulation
stimulator
interferon
genes
(STING)
triggered
by
generated
ROS
Mn2+
from
NPMCA,
respectively,
leading
activation
antitumor
immune
response.
The
potency
response
further
reinforced
reducing
accumulation
activated
ADA.
As
result,
enables
SDT-cooperated
immunotherapy,
showing
obviously
improved
therapeutic
efficacy
inhibit
growths
bilateral
tumors,
primary
are
tissues.
Advanced Materials,
Journal Year:
2023,
Volume and Issue:
36(4)
Published: Aug. 29, 2023
Photodynamic
therapy
(PDT),
which
utilizes
type
I
photoreactions,
has
great
potential
as
an
effective
cancer
treatment
because
of
its
hypoxia-tolerant
superiority
over
the
commonly
used
II
pathway.
A
few
photosensitizers
are
exploited;
however,
they
majorly
induce
cytotoxicity
and
possess
poor
tumor
specificity
low-efficient
theranostics.
To
resolve
this
issue,
herein
aminopeptidase
N
(APN)-activated
phototheranostic
probe
(CyA)
is
reported
for
anti-hypoxic
PDT
in
conjunction
with
immunotherapy
treatment.
CyA
can
specifically
activate
near-infrared
fluorescence,
photoacoustic
signals,
phototoxicity
following
APN-induced
substrate
cleavage
subsequent
generation
active
molecules
(such
CyBr).
endows
specific
imaging
capabilities
toward
cells
overexpressing
APN
under
both
normoxia
hypoxia.
In
addition,
locally
activatable
induces
systemic
antitumor
immune
responses.
More
importantly,
integration
localized
activated
evokes
enhanced
therapeutic
effects
improved
inhibition
efficiency
live
mice
compared
individual
treatments.
This
study
aims
to
present
combination
therapy.
Advanced Materials,
Journal Year:
2023,
Volume and Issue:
35(33)
Published: May 11, 2023
Inducing
immunogenic
cell
death
(ICD)
by
sonodynamic
therapy
(SDT)
is
promising
for
cancer
immunotherapy,
which
however
inefficient
due
to
oxygen
depletion
that
compromises
SDT
effect
and
mediates
recruitment
of
immunosuppressive
myeloid-derived
suppressor
cells
(MDSCs).
The
fabrication
sono-activatable
semiconducting
polymer
nanopartners
(SPNTi
)
simultaneously
augment
ICD
alleviate
MDSCs
immunotherapy
reported.
A
polymer,
hydrophobic
hypoxia-responsive
tirapazamine
(TPZ)-conjugate,
MDSC-targeting
drug
(ibrutinib)
are
encapsulated
inside
such
SPNTi
with
surface
shell
a
singlet
(1
O2
)-cleavable
amphiphilic
polymer.
TPZ
ibrutinib
serve
as
partners
enlarge
immunotherapeutic
effect.
Upon
sono-activation,
generate
1
break
-cleavable
polymers
in
situ
liberations
TPZ-conjugate
tumor
sites,
consumed
create
severe
hypoxic
microenvironment,
which,
activated
augmenting
action,
while
alleviates
promoting
antitumor
immunological
In
bilateral
mouse
model,
-mediated
results
growth
restraints
primary
distant
tumors
noteworthy
precaution
metastases.
This
study
thus
provides
strategy
high
precision
safety
via
overcoming
post-treatment
hypoxia
targeting
MDSCs.