ACS Nano,
Год журнала:
2024,
Номер
19(1), С. 837 - 851
Опубликована: Дек. 28, 2024
Tumor-specific
cytotoxic
T
cell
immunity
is
critically
dependent
on
effective
antigen
presentation
and
sustained
signal
transduction.
However,
this
immune
response
frequently
compromised
by
the
inherently
low
immunogenicity
of
breast
cancer
deficiency
in
major
histocompatibility
complex
class
I
(MHC-I)
expression.
Herein,
a
chimeric
peptide-engineered
stoichiometric
polyprodrug
(PDPP)
fabricated
to
potentiate
response,
characterized
high
drug
loading
capacity
precise
ratio,
which
immunogenic
death
(ICD)
inducer
protoporphyrin
IX
(PpIX)
epigenetic
decitabine
(DAC)
are
condensed
into
called
PpIX-DAC.
Furthermore,
programmed
ligand
1
(PD-L1)
targeting
peptide
sequence
(CVRARTR)
conjugated
onto
DSPE-PEG2000-Mal
for
encapsulation
PpIX-DAC,
thereby
enhancing
cancer-targeted
delivery.
PDPP
exerts
its
antitumor
effects
through
photodynamic
therapy
(PDT),
ablating
cells
while
concurrently
inducing
release
damage-associated
molecular
patterns
(DAMPs)
boost
tumor
immunogenicity.
Additionally,
can
upregulate
MHC-I
expression
via
modulation,
synergistically
augmenting
together
with
PD-L1
blockade.
In
short,
induces
robust
immunity,
causing
eradication
primary
metastatic
cancer.
This
study
may
inspire
development
nanomedicine
clinical
translation.
Abstract
The
chemo‐regulation
abilities
of
chemotherapeutic
medications
are
appealing
to
address
the
low
immunogenicity,
immunosuppressive
lactate
microenvironment,
and
adaptive
immune
resistance
colorectal
cancer.
In
this
work,
proteolysis
targeting
chimera
(PROTAC)
BRD4
(dBET57)
is
found
downregulate
cancer
glycolysis
through
transcription
inhibition
c‐Myc,
which
also
inhibits
expression
programmed
death
ligand
1
(PD‐L1)
reverse
evasion
avoid
resistance.
Based
on
this,
self‐delivery
nano‐PROTACs
(designated
as
DdLD
NPs)
further
fabricated
by
self‐assembly
doxorubicin
(DOX)
dBET57
with
assistance
DSPE‐PEG
2000
.
NPs
can
improve
stability,
intracellular
delivery,
tumor
accumulation
DOX
dBET57.
Meanwhile,
effect
efficiently
destroy
cells
trigger
a
robust
immunogenic
cell
(ICD).
More
importantly,
effects
inhibit
reduce
production,
PD‐L1
degradation.
Taking
advantages
chemotherapy
ability,
systemically
activated
antitumor
immunity
suppress
primary
metastatic
progression
without
inducing
any
systemic
side
effects.
Such
may
provide
new
insight
for
chemotherapy‐enabled
immunotherapy.
ACS Nano,
Год журнала:
2024,
Номер
18(35), С. 23827 - 23841
Опубликована: Авг. 20, 2024
Carrier-free
nanodrugs
with
extraordinary
active
pharmaceutical
ingredient
(API)
loading
(even
100%),
avoidable
carrier-induced
toxicity,
and
simple
synthetic
procedures
are
considered
as
one
of
the
most
promising
candidates
for
disease
theranostics.
Substantial
studies
commercial
success
"carrier-free"
nanocrystals
have
demonstrated
their
strong
clinical
potential.
However,
practical
translations
remain
challenging
impeded
by
unpredictable
assembly
processes,
insufficient
delivery
efficiency,
an
unclear
in
vivo
fate.
In
this
Perspective,
we
systematically
outline
contemporary
emerging
carrier-free
based
on
diverse
APIs,
well
highlight
opportunities
challenges
translation.
Looking
ahead,
further
improvements
design
preparation,
drug
delivery,
efficacy,
safety
nanomedicines
essential
to
facilitate
translation
from
bench
bedside.
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 14, 2025
Abstract
Designing
drugs
to
intelligently
respond
different
ratio
of
biological
electron
donors/receptors
in
cancer
cells
and
normal
is
a
promising
strategy
achieve
highly
effective
less
toxic
chemotherapy.
Herein
by
employing
metal
center
active
the
selenium‐containing
electrophilic
drug
Ru(phtpy‐NO
2
)(phenSe)Cl
(
RuSe
)
with
strongly
polarization
characteristics
are
synthesized
which
can
efficiently
shuttle
electrons
from
donors
convert
oxidative
stress.
The
rate
transfer
at
selenium
1.81
times
higher
cell
environments
compared
environments.
This
results
being
14.98
more
lethal
than
cells.
Experimental
demonstrate
that
transport
process
carried
out
via
radicals
intermediate
positively
correlated
properties
atoms.
transports
bioactive
generate
large
number
superoxide
anions
leading
DNA
damage
decrease
mitochondrial
membrane
potential
further
activates
p53
signaling
pathway
amplifies
cell‐killing
effect
after
transporting
electrons.
work
provides
new
avenue
for
design
efficient
chemotherapeutic
agents.
International Journal of Biological Macromolecules,
Год журнала:
2024,
Номер
275, С. 133680 - 133680
Опубликована: Июль 4, 2024
Proteolysis
targeting
chimeras
(PROTACs)
can
use
the
intrinsic
protein
degradation
system
in
cells
to
degrade
pathogenic
target
proteins,
and
are
currently
a
revolutionary
frontier
of
development
strategy
for
tumor
treatment
with
small
molecules.
However,
poor
water
solubility,
low
cellular
permeability,
off-target
side
effects
most
PROTACs
have
prevented
them
from
passing
preclinical
research
stage
drug
development.
This
requires
appropriate
delivery
systems
overcome
these
challenging
hurdles
ensure
precise
towards
site.
Therefore,
combination
multifunctional
will
open
up
new
directions
targeted
proteins.
In
this
review,
we
systematically
reviewed
design
principles
recent
advances
various
systems.
Moreover,
constructive
strategies
developing
were
proposed
comprehensively.
review
aims
deepen
understanding
drugs
promote
further
system.
Nanomedicine,
Год журнала:
2025,
Номер
unknown, С. 1 - 12
Опубликована: Янв. 20, 2025
Introduction
Colorectal
cancer
(CRC)
remains
a
serious
threat
to
humans
worldwide.
In
this
study,
we
used
bibliometric
analysis
of
the
scientific
literature
assess
trends
and
prospects
nanotechnology
applications
in
CRC.
Advanced Functional Materials,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 14, 2025
Abstract
Tuning
the
oxidative
stress‐defense
system
plays
a
vital
role
in
treatment
of
breast
tumors.
In
this
study,
pyropheophorbide‐a
(PPa)‐based
prodrug
nanoassembly
is
constructed
by
linking
PPa
with
furoxan,
cysteine‐depleting
nitric
oxide
(NO)
donor,
through
disulfide
bond.
The
as‐prepared
(NOSP)
can
assemble
distearoyl
phosphoethanolamine‐PEG
2000
(DSPE‐PEG
)
to
form
nanoassemblies
aqueous
media.
Following
internalization
tumor
cells,
NOSP
respond
cysteine
(Cys)
and
induce
NO
release
activate
endogenous
matrix
metalloproteinases
(MMP‐1,
‐2),
leading
collagen
degradation
improved
drug
delivery.
addition,
Cys
consumption
impede
biosynthesis
glutathione
(GSH),
while
react
high
levels
intracellular
GSH
within
seconds,
thus
synergizing
photodynamic
therapy
against
tumors
distant
metastasis.
