Macromolecular Rapid Communications,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 4, 2025
Targeted
protein
degradation
(TPD)
using
the
proteolysis-targeting
chimeras
(PROTACs)
is
emerging
as
a
revolutionary
technology,
offering
potential
strategy
for
cancer
treatment
by
inducing
of
overexpressed
oncogenic
proteins
in
tumors.
PROTACs
function
recruiting
E3
ligases
and
utilizing
ubiquitin-proteasome
pathway
(UPS)
to
catalyze
target
proteins.
Compared
traditional
small
molecules
inhibitors,
exhibit
enhanced
selectivity,
ability
overcome
drug
resistance,
traditionally
deemed
"undruggable".
However,
poor
water
solubility
low
cellular
permeability
significantly
limit
their
pharmacokinetic
properties,
while
systemic
toxicity
may
hinder
clinical
application.
To
address
these
limitations,
strategies
that
integrate
with
delivery
systems
are
gaining
attention.
This
review
summarizes
latest
advancements
various
enhance
vivo
efficacy
reduce
off-target
effects
PROTACs,
including
prototype
nanoparticles,
covalent
modification-based
prodrug
strategies,
innovative
multi-headed
designs,
microneedle
systems,
discussing
design
principles
associated
challenges.
The
combination
potent
multifunctional
holds
promise
accelerating
translation
improving
therapeutic
treatment.
Advanced Materials,
Год журнала:
2024,
Номер
36(21)
Опубликована: Фев. 16, 2024
Proteolysis
targeting
chimera
(PROTAC)
has
recently
emerged
as
a
promising
strategy
for
inducing
post-translational
knockdown
of
target
proteins
in
disease
treatment.
The
degradation
bromodomain-containing
protein
4
(BRD4),
an
essential
nuclear
gene
transcription,
induced
by
PROTAC
is
proposed
epigenetic
approach
to
treat
breast
cancer.
However,
the
poor
membrane
permeability
and
indiscriminate
distribution
vivo
results
low
bioavailability,
limiting
its
development
application.
Herein,
nano
"targeting
chimera"
(abbreviated
L@NBMZ)
consisting
BRD4-PROTAC
combined
with
photosensitizer,
serve
first
augmenter
photo-driven
pyroptosis
cancer,
developed.
With
excellent
BRD4
ability,
high
biosafety,
biocompatibility,
L@NBMZ
blocks
transcription
degrading
through
proteasomes
vivo,
surprisingly,
induces
cleavage
caspase-3.
This
type
caspase-3
synergistically
amplified
light
irradiation
presence
photosensitizers,
leading
efficient
pyroptosis.
Both
vitro
outcomes
demonstrate
remarkable
anti-cancer
efficacy
this
augmenter,
which
significantly
inhibits
lung
metastasis
cancer
vivo.
Thus,
photo-PROTAC
construction
may
pave
new
way
expanding
applications
within
paradigms.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(30)
Опубликована: Май 3, 2024
Eosinophils
are
important
immune
effector
cells
that
affect
T
cell-mediated
antitumor
immunity.
However,
the
low
frequency
and
restrained
activity
of
eosinophils
restricted
outcome
cancer
immunotherapies.
We
herein
report
an
eosinophil-activating
semiconducting
polymer
nanoparticle
(SPNe)
to
improve
photodynamic
tumor
immunogenicity,
modulate
eosinophil
chemotaxis,
reinvigorate
T-cell
immunity
for
activated
photo-immunotherapy.
SPNe
comprises
amphiphilic
a
dipeptidyl
peptidase
4
(DPP4)
inhibitor
sitagliptin
via
Macromolecular Rapid Communications,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 4, 2025
Targeted
protein
degradation
(TPD)
using
the
proteolysis-targeting
chimeras
(PROTACs)
is
emerging
as
a
revolutionary
technology,
offering
potential
strategy
for
cancer
treatment
by
inducing
of
overexpressed
oncogenic
proteins
in
tumors.
PROTACs
function
recruiting
E3
ligases
and
utilizing
ubiquitin-proteasome
pathway
(UPS)
to
catalyze
target
proteins.
Compared
traditional
small
molecules
inhibitors,
exhibit
enhanced
selectivity,
ability
overcome
drug
resistance,
traditionally
deemed
"undruggable".
However,
poor
water
solubility
low
cellular
permeability
significantly
limit
their
pharmacokinetic
properties,
while
systemic
toxicity
may
hinder
clinical
application.
To
address
these
limitations,
strategies
that
integrate
with
delivery
systems
are
gaining
attention.
This
review
summarizes
latest
advancements
various
enhance
vivo
efficacy
reduce
off-target
effects
PROTACs,
including
prototype
nanoparticles,
covalent
modification-based
prodrug
strategies,
innovative
multi-headed
designs,
microneedle
systems,
discussing
design
principles
associated
challenges.
The
combination
potent
multifunctional
holds
promise
accelerating
translation
improving
therapeutic
treatment.
