Canonical
phototherapeutics
have
several
limitations,
including
a
lack
of
tumor
selectivity,
nondiscriminatory
phototoxicity,
and
hypoxia
aggravation.
The
microenvironment
(TME)
is
characterized
by
hypoxia,
acidic
pH,
high
levels
H2
O2
,
GSH,
proteases.
To
overcome
the
shortcomings
canonical
phototherapy
achieve
optimal
theranostic
effects
with
minimal
side
effects,
unique
TME
characteristics
are
employed
in
development
phototherapeutic
nanomedicines.
In
this
review,
effectiveness
three
strategies
for
developing
advanced
based
on
various
examined.
first
strategy
involves
targeted
delivery
to
tumors
assistance
TME-induced
nanoparticle
disassembly
or
surface
modification.
second
near-infrared
absorption
increase-induced
activation
triggered
factors.
third
enhancing
therapeutic
efficacy
ameliorating
TME.
functionalities,
working
principles,
significance
applications
highlighted.
Finally,
possible
challenges
future
perspectives
further
discussed.
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
Canonical
phototherapeutics
have
several
limitations,
including
a
lack
of
tumor
selectivity,
nondiscriminatory
phototoxicity,
and
hypoxia
aggravation.
The
microenvironment
(TME)
is
characterized
by
hypoxia,
acidic
pH,
high
levels
H2
O2
,
GSH,
proteases.
To
overcome
the
shortcomings
canonical
phototherapy
achieve
optimal
theranostic
effects
with
minimal
side
effects,
unique
TME
characteristics
are
employed
in
development
phototherapeutic
nanomedicines.
In
this
review,
effectiveness
three
strategies
for
developing
advanced
based
on
various
examined.
first
strategy
involves
targeted
delivery
to
tumors
assistance
TME-induced
nanoparticle
disassembly
or
surface
modification.
second
near-infrared
absorption
increase-induced
activation
triggered
factors.
third
enhancing
therapeutic
efficacy
ameliorating
TME.
functionalities,
working
principles,
significance
applications
highlighted.
Finally,
possible
challenges
future
perspectives
further
discussed.
