Angewandte Chemie International Edition,
Journal Year:
2021,
Volume and Issue:
61(8)
Published: Dec. 20, 2021
Protease
inhibitors
can
modulate
intratumoral
metabolic
processes
to
reprogram
the
immunosuppressive
tumor
microenvironment
(TME),
which
however
suffer
from
limited
efficacy
and
off-targeted
side
effects.
We
report
smart
nano-proteolysis
targeting
chimeras
(nano-PROTACs)
with
phototherapeutic
ablation
cancer-specific
protein
degradation
TME
for
photo-metabolic
cancer
immunotherapy.
This
nano-PROTAC
has
a
semiconducting
polymer
backbone
linked
cyclooxygenase
1/2
(COX-1/2)-targeting
PROTAC
peptide
(CPP)
via
cathepsin
B
(CatB)-cleavable
segment.
CPP
be
activated
by
tumor-overexpressed
CatB
induce
of
COX-1/2
ubiquitin-proteasome
system.
The
persistent
depletes
their
metabolite
prostaglandin
E2
is
responsible
activation
immune
suppressor
cells.
Such
strategy
synergized
phototherapy
specifically
reprograms
reinvigorates
antitumor
immunity.
Bioactive Materials,
Journal Year:
2022,
Volume and Issue:
21, P. 299 - 312
Published: Sept. 13, 2022
To
improve
the
response
rate
of
immune
checkpoint
inhibitors
such
as
anti-PD-L1
antibody
in
immunosuppressive
cancers
like
triple-negative
breast
cancer
(TNBC),
induction
immunogenic
cell
death
(ICD)
at
tumor
sites
can
increase
antigenicity
and
adjuvanticity
to
activate
microenvironment
so
that
tumors
become
sensitive
intervention
inhibitors.
Herein,
a
self-amplified
biomimetic
nanosystem,
mEHGZ,
was
constructed
by
encapsulation
epirubicin
(EPI),
glucose
oxidase
(Gox)
hemin
ZIF-8
nanoparticles
coating
with
calreticulin
(CRT)
over-expressed
membrane.
EPI
acts
an
ICD
inducer,
Gox
medicate
cascade
generation
reactive
oxygen
species
(ROS)
strengthen
effect,
CRT-rich
membrane
"eat
me"
signal
promote
presentation
released
antigens
dendritic
cells
(DCs)
invoke
tumor-immunity
cycle.
The
delivery
system
displays
amplified
effect
via
oxidation,
hydroxyl
radical
glutathione
(GSH)
depletion.
induced
potent
promotes
DCs
maturation
cytotoxic
T
lymphocytes
(CTLs)
infiltration,
reversing
immunoresponsive
one.
Treatment
nanosystem
combination
results
distinctive
inhibition
growth
lung
metastasis,
supporting
significantly
boost
therapeutic
efficacy
antibody.
This
nanoplatform
offers
promising
means
raising
Advanced Materials,
Journal Year:
2022,
Volume and Issue:
34(28)
Published: May 7, 2022
Despite
the
great
promises
of
sonodynamic
therapy
(SDT)
in
combination
cancer
therapy,
its
clinical
applications
are
hindered
by
"always-on"
pharmacological
activities
therapeutic
agents
and
lack
efficient
sonosensitizers.
Herein,
development
semiconducting
polymers
as
sonosensitizers
further
sono-immunotherapeutic
nanobodies
(SPNAb
)
for
activatable
sono-immunotherapy
reported.
Conjugation
anti-CTLA-4
antibodies
onto
polymer
nanoparticles
through
a
1
O2
-cleavable
linker
affords
SPNAb
with
relatively
low
CTLA-4
binding
affinity.
Upon
sono-irradiation,
generates
not
only
to
elicit
effect
induce
immunogenic
cell
death,
but
also
release
trigger
situ
checkpoint
blockade.
Such
synergistic
action
mediated
modulates
tumoricidal
function
T-cell
immunity
promoting
proliferation
cytotoxic
T
lymphocytes
depleting
immunosuppressive
regulatory
cells,
resulting
effective
tumor
regression,
metastasis
inhibition,
durable
immunological
memory,
prevention
relapse.
Therefore,
this
study
represents
proof-of-concept
strategy
using
precise
spatiotemporal
control
over
immunotherapy.
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: Oct. 19, 2022
Cell
membrane
(CM)
coating
technology
is
increasingly
being
applied
in
nanomedicine,
but
the
entire
procedure
including
adsorption,
rupture,
and
fusion
not
completely
understood.
Previously,
we
showed
that
majority
of
biomimetic
nanoparticles
(NPs)
were
only
partially
coated,
mechanism
underlying
this
partial
remains
unclear,
which
hinders
further
improvement
technique.
Here,
show
an
intermediate
state
due
to
adsorption
CM
fragments
or
vesicles,
latter
could
eventually
be
ruptured
under
external
force.
Such
difficult
self-repair
achieve
full
limited
fluidity.
Building
on
our
understanding
detailed
process,
develop
a
general
approach
for
fixing
coating:
phospholipid
introduced
as
helper
increase
fluidity,
promoting
final
lipid
patches.
The
NPs
coated
with
have
high
ratio
(~23%)
exhibit
enhanced
tumor
targeting
ability
comparison
traditionally
(full
~6%).
Our
results
provide
mechanistic
basis
towards
enhancing
accumulation.
Advanced Materials,
Journal Year:
2022,
Volume and Issue:
34(30)
Published: June 7, 2022
Osteoarthritis
(OA)
is
a
low-grade
inflammatory
and
progressive
joint
disease,
its
progression
closely
associated
with
an
imbalance
in
M1/M2
synovial
macrophages.
Repolarizing
pro-inflammatory
M1
macrophages
into
the
anti-inflammatory
M2
phenotype
emerging
as
strategy
to
alleviate
OA
but
compromised
by
unsatisfactory
efficiency.
In
this
study,
reprogramming
of
mitochondrial
dysfunction
pioneered
camouflaged
meta-Defensome,
which
can
transform
high
efficiency
82.3%.
The
meta-Defensome
recognizes
activated
via
receptor-ligand
interactions
accumulates
mitochondria
through
electrostatic
attractions.
These
meta-Defensomes
are
macrophage-membrane-coated
polymeric
nanoparticles
decorated
dual
ligands
co-loaded
S-methylisothiourea
MnO2
.
Meta-Defensomes
demonstrated
successfully
reprogram
metabolism
scavenging
reactive
oxygen
species
inhibiting
NO
synthase,
thereby
increasing
transcription
factor
A
expression
restoring
aerobic
respiration.
Furthermore,
intravenously
injected
collagenase-induced
osteoarthritis
mice
effectively
suppress
inflammation
early
OA,
evident
from
Research
Society
International
score.
Therefore,
serve
novel
practical
approach
repolarize
promising
therapeutic
agent
for
impeding
tclinic.
Journal of Nanobiotechnology,
Journal Year:
2022,
Volume and Issue:
20(1)
Published: Feb. 17, 2022
No
prominent
advancements
in
osteosarcoma
(OS)
treatment
have
been
made
the
past
20
years.
Although
photodynamic
therapy
(PDT)
is
an
emerging
technique
for
cancer
therapy,
lack
of
targeted
photosensitizers
OS
severely
limits
its
applications.
In
this
study,
we
constructed
a
potential
theranostic
nanoplatform
by
using
(poly
(lactic-co-glycolic)
acid
(PLGA)
nanoparticles
(NPs)
encapsulating
IR780
into
shell
(PLGA-IR780
NPs),
which
were
further
camouflaged
with
human
cell
membranes
from
HOS
line
(MH-PLGA-IR780
NPs).
These
NPs
showed
capacity
homologous
targeting
excellent
photoacoustic
(PA)/fluorescence
(FL)
imaging
ability.
Benefitting
their
capacity,
MH-PLGA-IR780
obviously
promoted
endocytosis
vitro
and
tumor
accumulation
vivo,
could
improve
PDT
performance
under
near-infrared
(NIR)
irradiation.
addition,
to
PA/FL
dual-mode
ability,
had
advantages
penetrating
deeper
tissues
real-time
dynamic
distribution
monitoring
laid
foundation
clinical
applications
OS.
Moreover,
demonstrated
that
guided
significantly
induce
cells
apoptosis
ferroptosis
via
excessive
reactive
oxygen
species
(ROS),
determined
anticancer
molecular
mechanism
was
triggered
release
cytochrome
c-activated
mitochondrial
(endogenous
apoptosis),
caused
activation
nuclear
receptor
coactivator
4
(NCOA4)-mediated
ferritinophagy
inactivation
glutathione
peroxidase
(GPX4),
synergistically
leading
Lipid-ROS
Lipid
peroxides
(LPOs).
Concurrently,
NPs-guided
also
obvious
inhibitory
effect
on
growth
vivo.
results
suggest
targeting-based
provides
effective
method
contributes
new
promising
approach
therapy.
Exploration,
Journal Year:
2023,
Volume and Issue:
3(1)
Published: Jan. 5, 2023
Nanomaterials
are
promising
carriers
to
improve
the
bioavailability
and
therapeutic
efficiency
of
drugs
by
providing
preferential
drug
accumulation
at
their
sites
action,
but
delivery
efficacy
is
severely
limited
a
series
biological
barriers,
especially
mononuclear
phagocytic
system
(MPS)-the
first
major
barrier
encountered
systemically
administered
nanomaterials.
Herein,
current
strategies
for
evading
MPS
clearance
nanomaterials
summarized.
First,
engineering
methods
including
surface
modification,
cell
hitchhiking,
physiological
environment
modulation
reduce
explored.
Second,
disabling
blockade,
suppression
macrophage
phagocytosis,
macrophages
depletion
examined.
Last,
challenges
opportunities
in
this
field
further
discussed.
Exploration,
Journal Year:
2023,
Volume and Issue:
3(2)
Published: March 16, 2023
Abstract
Heterogeneous
cells
are
the
main
feature
of
tumors
with
unique
genetic
and
phenotypic
characteristics,
which
can
stimulate
differentially
progression,
metastasis,
drug
resistance.
Importantly,
heterogeneity
is
pervasive
in
human
malignant
tumors,
identification
degree
tumor
individual
progression
a
critical
task
for
treatment.
However,
current
medical
tests
cannot
meet
these
needs;
particular,
need
noninvasive
visualization
single‐cell
heterogeneity.
Near‐infrared
II
(NIR‐II,
1000–1700
nm)
imaging
exhibits
an
exciting
prospect
non‐invasive
monitoring
due
to
high
temporal‐spatial
resolution.
More
importantly,
NIR‐II
displays
more
extended
tissue
penetration
depths
reduced
backgrounds
because
significantly
lower
photon
scattering
autofluorescence
than
traditional
near‐infrared
I
(NIR‐I)
imaging.
In
this
review,
we
summarize
systematically
advances
made
imaging,
especially
detection
as
well
As
visual
inspection
modality,
shows
promising
prospects
understanding
differences
envisioned
have
potential
be
used
clinically.
