Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(34), P. 24177 - 24187
Published: Aug. 14, 2024
Despite
significant
progress
achieved
in
artificial
self-sorting
solution,
operating
the
body
remains
a
considerable
challenge.
Here,
we
report
an
vivo
peptide
system
via
situ
assembly
evolution
for
combined
cancer
therapy.
The
ACS Nano,
Journal Year:
2022,
Volume and Issue:
16(11), P. 18849 - 18862
Published: Oct. 24, 2022
Single-atom
nanozymes
(SAzymes),
with
individually
isolated
metal
atom
as
active
sites,
have
shown
tremendous
potential
enzyme-based
drugs
for
enzymatic
therapy.
However,
using
SAzymes
in
tumor
theranostics
remains
challenging
because
of
deficient
activity
and
insufficient
endogenous
H2O2.
We
develop
an
external-field-enhanced
catalysis
by
atom-level
engineered
FeN4-centered
nanozyme
(FeN4-SAzyme)
radio-enzymatic
This
FeN4-SAzyme
exhibits
peroxidase-like
capable
catalyzing
H2O2
into
hydroxyl
radicals
converting
single-site
FeII
species
to
FeIII
subsequent
glutathione
oxidase-like
activity.
Density
functional
theory
calculations
are
used
rationalize
the
origin
self-cascade
Importantly,
X-rays
can
improve
overall
cascade
reaction
process
via
promoting
conversion
frequency
FeII/FeIII.
As
a
producer,
natural
glucose
oxidase
is
further
decorated
onto
surface
yield
final
construct
GOD@FeN4-SAzyme.
The
resulting
GOD@FeN4-SAzyme
not
only
supplies
situ
continuously
produce
highly
toxic
but
also
induces
localized
deposition
radiation
dose,
subsequently
inducing
intensive
apoptosis
ferroptosis
vitro.
Such
synergistic
effect
radiotherapy
therapy
allows
improved
growth
inhibition
minimal
side
effects
vivo.
Collectively,
this
work
demonstrates
introduction
external
fields
enhance
enzyme-like
performance
without
changing
their
properties
highlights
robust
therapeutic
self-supplying
amplifying
reactions
address
limitations
treatment.
Advanced Materials,
Journal Year:
2022,
Volume and Issue:
34(45)
Published: Aug. 30, 2022
To
improve
the
therapeutic
effect
of
sonodynamic
therapy
(SDT),
more
effective
and
stable
sonosensitizers
strategies
are
still
required.
A
covalent
organic
framework
(COF)
sonosensitizer
is
developed
by
using
a
new
nanoscale
COF
preparation
strategy.
This
strategy
uses
molecular
etching
based
on
imine
exchange
reaction
to
etch
bulk
into
nanoparticles
has
universal
applicability
imine-bond-based
COF.
The
regular
structure
can
prevent
loss
performance
caused
aggregation
porphyrin
molecules
chemical
stability
unit.
In
addition,
coordination
Fe3+
endows
nanoparticle
with
chemodynamic
glutathione
consumption
ability.
combination
enhanced
SDT
α-PD-L1
antibody
achieves
good
antitumor
effect.
innovative
provides
avenue
for
clinical
therapy.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(15), P. 10753 - 10766
Published: April 5, 2024
Proteolysis
targeting
chimera
(PROTAC)
technology
is
an
innovative
strategy
for
cancer
therapy,
which,
however,
suffers
from
poor
delivery
and
limited
capability
protein
of
interest
(POI)
degradation.
Here,
we
report
a
the
in
situ
formulation
antineoplastic
Supra-PROTACs
via
intracellular
sulfatase-responsive
assembly
peptides.
Coassembling
sulfated
peptide
with
two
ligands
binding
to
ubiquitin
VHL
Bcl-xL
leads
formation
pro-Supra-PROTAC,
which
ratio
rationally
optimized
based
on
their
affinity.
The
resulting
pro-Supra-PROTAC
precisely
undergoes
enzyme-responsive
into
nanofibrous
cells
overexpressing
sulfatase.
Mechanistic
studies
reveal
that
pro-Supra-PROTACs
selectively
cause
apparent
cytotoxicity
through
degradation
activation
caspase-dependent
apoptosis,
during
ligand
improves
bioactivity
POI
cell
death.
In
vivo
show
enhanced
tumor
accumulation
retention
pro-Supra-PROTACs,
as
well
inhibiting
growth
excellent
biosafety
when
coadministrating
chemodrugs.
Our
findings
provide
new
approach
enzyme-regulated
peptides
living
development
PROTACs
high
delivering
efficiency.
Journal of the American Chemical Society,
Journal Year:
2021,
Volume and Issue:
143(31), P. 12025 - 12037
Published: July 28, 2021
The
ability
of
nanomotors
to
promote
the
deep
penetration
themselves
and
loaded
drugs
in
diseased
tissues
has
been
proposed
confirmed.
However,
whether
such
motion
behavior
can
also
micrometer-sized
immune
cells
microenvironment,
which
is
important
for
immunotherapy
some
diseases,
not
mentioned.
Herein,
we
construct
a
nitric
oxide
(NO)-driven
nanomotor
that
move
tumor
focusing
on
its
role
NO,
beneficial
product
released
during
movement
from
this
kind
nanomotor,
regulating
infiltration
activity
cells.
It
be
found
drug-loaded
with
both
NO-releasing
motility
normalization
vasculature
system
degradation
intrinsic
extracellular
matrix
(ECM),
significantly
improve
T
vivo.
efficiency
T-cell
tissue
vivo
increased
2.1
28.2%.
Both
subcutaneous
intraperitoneal
implantation
models
validate
excellent
antitumor
effect
NO-driven
nanomotors.
This
combination
power
source
their
physiological
function
offers
design
idea
therapeutic
agents
future
many
diseases.
Journal of the American Chemical Society,
Journal Year:
2022,
Volume and Issue:
144(13), P. 5769 - 5783
Published: March 11, 2022
The
receptor–ligand
interactions
in
cells
are
dynamically
regulated
by
modulation
of
the
ligand
accessibility.
In
this
study,
we
utilize
size-tunable
magnetic
nanoparticle
aggregates
ordered
at
both
nanometer
and
atomic
scales.
We
flexibly
anchor
tunable
sizes
over
cell-adhesive
RGD
(Arg-Gly-Asp)-active
material
surface
while
maintaining
density
dispersed
ligands
accessible
to
macrophages
constant.
Lowering
dispersity
increasing
aggregate
size
constant
facilitates
binding
integrin
receptors
ligands,
which
promotes
adhesion
macrophages.
high
dispersity,
distant
manipulation
lift
(which
increases
accessibility)
stimulates
available
under
augment
macrophage
adhesion-mediated
pro-healing
polarization
vitro
vivo.
low
control
drop
decreases
repels
away
from
aggregates,
thereby
suppressing
adhesion,
inflammatory
polarization.
Here,
present
"accessible
dispersity"
as
a
novel
fundamental
parameter
that
regulates
binding,
can
be
reversibly
manipulated
decreasing
Limitless
tuning
dimensions
morphology
offer
further
insight
into
regulation
host
cells.
Journal of the American Chemical Society,
Journal Year:
2022,
Volume and Issue:
144(15), P. 6907 - 6917
Published: April 7, 2022
Enzyme-regulated
in
situ
self-assembly
of
peptides
represents
one
versatile
strategy
the
creation
theranostic
agents,
which,
however,
is
limited
by
strong
dependence
on
enzyme
overexpression.
Herein,
we
reported
self-amplifying
assembly
precisely
macrophages
associated
with
expression
for
improving
anti-inflammatory
efficacy
conventional
drugs.
The
assembling
system
was
created
via
coassembling
an
enzyme-responsive
peptide
its
derivative
functionalized
a
protein
ligand.
Reduction
NAD(P)H
quinone
dehydrogenase
1
(NQO1)
led
to
formation
nanofibers
high
affinity
protein,
thereby
facilitating
NQO1
expression.
improved
level
conversely
promoted
into
nanofibers,
thus
establishing
amplifying
relationship
between
and
macrophages.
Utilization
as
vehicles
drug
dexamethasone
allowed
passive
targeting
delivery
acute
injured
lungs.
Both
vitro
vivo
studies
confirmed
capability
enhance
simultaneous
alleviation
reactive
oxygen
species
side
effect
downregulation
proinflammatory
cytokines.
Our
findings
demonstrate
manipulation
living
cells
regular
self-amplification
process,
providing
unique
supramolecular
agents
cells.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(20)
Published: March 20, 2023
Most
tumor
treatments
will
fail
when
ignoring
competition
and
cooperation
between
each
cancer
cell
its
microenvironment.
Inspired
by
game
theory,
therapeutic
agents
can
be
introduced
to
compete
for
intracellular
molecules
disrupt
the
cells.
Biomineralized
oxidized
(-)-epigallocatechin-3-o-gallate
(EGCG)-molybdenum
ion
coordination
nanoparticles
were
prepared
disrupting
redox
equilibria
simultaneously
reacting
with
GSH
in
a
Michael
addition
form
large
aggregates
that
mechanically
endosomal
plasma
membranes,
stimulating
pyroptosis
anti-tumor
immunological
responses
versatile
inhibition
of
different
types
tumors.
This
design
disrupts
immune
cells,
achieving
an
optimal
payoff
therapy.
Advanced Materials,
Journal Year:
2023,
Volume and Issue:
35(29)
Published: May 3, 2023
Tumor
cells
elicit
metabolic
reprogramming
to
establish
an
immunosuppressive
tumor
microenvironment
(TME)
for
escaping
from
immunosurveillance.
Therefore,
interrupting
the
adaptation
of
may
be
a
promising
strategy
TME
immunomodulation,
favoring
immunotherapy.
In
this
work,
tumor-specific
peroxynitrite
nanogenerator
APAP-P-NO
is
constructed
that
can
selectively
disrupt
homeostasis
in
melanoma
cells.
Stimulated
by
melanoma-characteristic
acid,
glutathione,
and
tyrosinase,
efficiently
generate
through
situ
coupling
produced
superoxide
anion
released
nitric
oxide.
Metabolomics
profiling
reveals
accumulated
induces
great
decrease
metabolites
tricarboxylic
acid
cycle.
Meanwhile,
glycolysis-produced
lactate
drops
sharply
both
intracellularly
extracellularly
under
stress.
Mechanistically,
impairs
activity
glyceraldehyde-3-phosphate
dehydrogenase
glucose
metabolism
S-nitrosylation.
The
alterations
effectively
reverse
evoke
potent
antitumor
immune
responses,
including
polarization
M2-like
macrophages
M1phenotype,
reduction
myeloid-derived
suppressor
regulatory
T
cells,
restoration
CD8+
cell
infiltration.
Combining
with
anti-PD-L1
achieves
significant
inhibition
against
primary
metastatic
melanomas
without
systemic
toxicities.
Collectively,
overproduction
approach
developed
possible
mechanism
peroxynitrite-mediated
immunomodulation
explored,
providing
new
facilitating
immunotherapy
sensitivity.