ACS Nano,
Год журнала:
2024,
Номер
18(42), С. 28502 - 28530
Опубликована: Окт. 8, 2024
Proteolysis
targeting
chimeras
(PROTACs)
represent
a
transformative
class
of
therapeutic
agents
that
leverage
the
intrinsic
protein
degradation
machinery
to
modulate
hemostasis
key
disease-associated
proteins
selectively.
Although
several
PROTACs
have
been
approved
for
clinical
application,
suboptimal
efficacy
and
potential
adverse
side
effects
remain
challenging.
Benefiting
from
enhanced
targeted
delivery,
reduced
systemic
toxicity,
improved
bioavailability,
nanomedicines
can
be
tailored
with
precision
integrate
which
hold
significant
facilitate
PROTAC
(nano-PROTACs)
translation
effects.
In
this
review,
we
provide
an
overview
recent
progress
in
convergence
nanotechnology
design,
leveraging
inherent
properties
nanomaterials,
such
as
lipids,
polymers,
inorganic
nanoparticles,
nanohydrogels,
proteins,
nucleic
acids,
precise
delivery.
Additionally,
discuss
various
categories
targets
insights
into
their
translational
potential,
alongside
challenges
need
addressed.
Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Фев. 11, 2025
Abstract
Accumulated
evidence
has
implicated
the
diverse
and
substantial
influence
of
lactate
on
cellular
differentiation
fate
regulation
in
physiological
pathological
settings,
particularly
intricate
conditions
such
as
cancer.
Specifically,
been
demonstrated
to
be
pivotal
molding
tumor
microenvironment
(TME)
through
its
effects
different
cell
populations.
Within
cells,
impacts
signaling
pathways,
augments
shuttle
process,
boosts
resistance
oxidative
stress,
contributes
lactylation.
In
various
populations,
interplay
between
immune
cells
governs
processes
differentiation,
response,
surveillance,
treatment
effectiveness.
Furthermore,
communication
stromal/endothelial
supports
basal
membrane
(BM)
remodeling,
epithelial-mesenchymal
transitions
(EMT),
metabolic
reprogramming,
angiogenesis,
drug
resistance.
Focusing
production
transport,
specifically
dehydrogenase
(LDH)
monocarboxylate
transporters
(MCT),
shown
promise
Inhibitors
targeting
LDH
MCT
act
both
suppressors
enhancers
immunotherapy,
leading
a
synergistic
therapeutic
effect
when
combined
with
immunotherapy.
The
review
underscores
importance
progression
provides
valuable
perspectives
potential
approaches
that
target
vulnerability
metabolism,
highlighting
Heel
Achilles
for
cancer
treatment.
Advanced Materials,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 10, 2025
Abstract
Cancer
immunotherapy,
which
leverages
immune
system
components
to
treat
malignancies,
has
emerged
as
a
cornerstone
of
contemporary
therapeutic
strategies.
Yet,
critical
concerns
about
the
efficacy
and
safety
cancer
immunotherapies
remain
formidable.
Nanotechnology,
especially
polymeric
nanoparticles
(PNPs),
offers
unparalleled
flexibility
in
manipulation‐from
chemical
composition
physical
properties
precision
control
nanoassemblies.
PNPs
provide
an
optimal
platform
amplify
potency
minimize
systematic
toxicity
broad
spectrum
immunotherapeutic
modalities.
In
this
comprehensive
review,
basics
polymer
chemistry,
state‐of‐the‐art
designs
from
physicochemical
standpoint
for
encompassing
vaccines,
situ
vaccination,
adoptive
T‐cell
therapies,
tumor‐infiltrating
cell‐targeted
antibodies,
cytokine
therapies
are
delineated.
Each
immunotherapy
necessitates
distinctively
tailored
design
strategies
nanoplatforms.
The
extensive
applications
PNPs,
investigation
their
mechanisms
action
enhanced
particularly
focused
on.
profiles
clinical
research
progress
discussed.
Additionally,
forthcoming
developments
emergent
trends
nano‐immunotherapeutics
poised
transform
treatment
paradigms
into
clinics
explored.
Nano Letters,
Год журнала:
2024,
Номер
24(28), С. 8741 - 8751
Опубликована: Июль 2, 2024
The
degradation
of
oncoproteins
mediated
by
proteolysis-targeting
chimera
(PROTAC)
has
emerged
as
a
potent
strategy
in
cancer
therapy.
However,
the
clinical
application
PROTACs
is
hampered
challenges
such
poor
water
solubility
and
off-target
adverse
effects.
Herein,
we
present
an
ultrasound
(US)-activatable
PROTAC
prodrug
termed
NP
Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Март 3, 2025
Abstract
Radiotherapy
(RT)
resistance
in
head
and
neck
squamous
cell
carcinoma
(HNSCC)
significantly
hampers
local
control
patient
prognosis.
This
study
investigated
the
efficacy
molecular
mechanisms
of
high-energy
X-ray-based
ultra-high
dose
rate
radiotherapy
(UHDR-RT)
overcoming
RT
resistance.
The
established
RT-resistant
HNSCC
lines
animal
models
were
subjected
to
UHDR-RT
or
conventional
(Conv-RT)
via
a
high-power
rhodotron
accelerator.
Cellular
assays
assessed
malignant
phenotype,
viability,
degree
DNA
damage,
whereas
vivo
evaluations
focused
on
tumor
proliferation
immune
microenvironment
(TiME).
Transcriptome
sequencing
Olink
proteomics
employed
explore
underlying
involved.
In
vitro
experiments
indicated
that
suppressed
radioresistant
invasion,
while
promoting
apoptosis
exacerbating
damage.
contrast,
its
radiosensitive
cells
was
comparable
Conv-RT.
studies
using
patient-derived
xenograft
nude
mice
demonstrated
only
partially
reversed
Transcriptomic
proteomic
analyses
C57BL/6J
revealed
predominant
role
TiME
modulating
reversing
radioresistance.
Immunofluorescence
flow
cytometry
confirmed
increased
CD8
+
T
an
M1/M2
macrophage
ratio
post-UHDR-RT.
Mechanistically,
activated
cells,
which
stimulated
M1
macrophages
through
paracrine
IFN-γ
signaling,
thereby
enhancing
activation.
Furthermore,
secreted
CXCL9,
turn
reactivated
forming
feedforward
loop
amplified
elucidates
dual
directly
inducing
damage
TiME,
highlighting
potential
treating
HNSCC.
Advanced Materials,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 3, 2025
Abstract
Glioblastoma
(GBM)
is
the
most
aggressive
subtype
of
primary
brain
tumors,
which
marginally
respond
to
standard
chemotherapy
due
blood‐brain
barrier
(BBB)
and
low
tumor
specificity
therapeutics.
Herein,
a
double‐layered
microneedle
(MN)
patch
rationally
engineered
by
integrating
acid
light
dual‐activatable
PROteolysis
TArgeting
Chimera
(PROTAC)
nanoparticles
self‐oxygenating
BSA‐MnO
2
(BM)
for
GBM
treatment.
The
MN
administrated
at
site
locally
deliver
PROTAC
prodrug
BM
nanoparticles.
are
rapidly
released
from
outer
layer
specifically
activated
in
acidic
intracellular
environment
cells.
Subsequently,
near‐infrared
activates
photosensitizer
produce
singlet
oxygen
(
1
O
)
through
photodynamic
therapy
(PDT),
thereby
triggering
spatiotemporally‐tunable
degradation
bromodomain
extraterminal
protein
4
(BRD4).
nanoparticles,
inner
MN,
serve
as
an
supply
station,
counteracts
hypoxia
converting
hydrogen
peroxide
(H
into
(O
),
thus
promoting
PDT
activation.
This
prodrug‐integrated
significantly
inhibits
growth
both
subcutaneous
orthotopic
models.
study
describes
first
strategy
highly
efficient
therapy,
potentially
advancing
precise
other
kinds
refractory
tumors.
As
a
member
of
BET
(bromodomain
and
extra-terminal)
protein
family,
BRD4
(bromodomain‑containing
4)
is
chromatin‑associated
that
interacts
with
acetylated
histones
actively
recruits
regulatory
proteins,
leading
to
the
modulation
gene
expression
chromatin
remodeling.
The
cellular
epigenetic
functions
implicate
normal
development,
fibrosis
inflammation.
has
been
suggested
as
potential
therapeutic
target
it
often
overexpressed
plays
critical
role
in
regulating
programs
drive
tumor
cell
proliferation,
survival,
migration
drug
resistance.
To
address
roles
cancer,
several
drugs
specifically
have
developed.
Inhibition
shown
promising
results
preclinical
models,
inhibitors
undergoing
clinical
trials
for
treatment
various
cancers.
Head
neck
squamous
carcinoma
(HNSCC),
heterogeneous
group
cancers,
remains
health
challenge
high
incidence
rate
poor
prognosis.
Conventional
therapies
HNSCC
cause
adverse
effects
patients.
Targeting
BRD4,
therefore,
represents
strategy
sensitize
chemo‑
radiotherapy
allowing
de‑intensification
current
regime
subsequent
reduced
side
effects.
However,
further
studies
are
required
fully
understand
underlying
mechanisms
action
order
determine
optimal
dosing
administration
BRD4‑targeted
patients
HNSCC.
Spatiotemporally
controlled
cancer
therapy
may
offer
great
advantages
in
precision
medicine,
but
still
remains
some
challenges
programmed
sequential
release
and
co-localization
of
components
at
target
sites.
Herein,
a
MXene-based
nanoprobe
(TCC@M)
is
meticulously
designed
by
engineering
photodynamically
activated
CRISPR-Cas9
cell
membrane-camouflaged
Ti
Biomaterials Science,
Год журнала:
2024,
Номер
12(14), С. 3686 - 3699
Опубликована: Янв. 1, 2024
A
near-infrared
light-controlled
PROTAC
delivery
nanodevice
achieves
enhanced
protein
degradation
efficiency
and
synergistic
therapeutic
efficacy
in
combination
with
NIR
light-triggered
photodynamic
therapy.
