Journal of Medicinal Chemistry,
Journal Year:
2022,
Volume and Issue:
65(6), P. 5057 - 5071
Published: Feb. 17, 2022
The
catalytic
properties
of
proteolysis
targeting
chimeras
(PROTACs)
may
lead
to
uncontrolled
off-tissue
target
degradation
that
causes
potential
toxicity,
limiting
their
clinical
applications.
precise
control
this
technology
in
a
tissue-selective
manner
can
minimize
the
toxicity.
Hypoxia
is
hallmark
most
solid
tumors,
accompanied
by
elevated
levels
nitroreductase
(NTR).
Based
on
character,
we
presented
type
NTR-responsive
PROTACs
selectively
degrade
proteins
interest
(POI)
tumor
tissues.
Compound
17-1
was
first
PROTAC
synthesized
incorporating
caging
group
Von
Hippel–Lindau
(VHL)
E3
ubiquitin
ligase
ligand.
It
could
be
activated
NTR
release
active
17
efficiently
EGFR
protein
and
subsequently
exert
antitumor
efficacy.
Thus,
general
strategy
for
induce
POI
tissues
established,
which
provided
generalizable
platform
development
NTR-controlled
achieve
selective
degradation.
Advanced Science,
Journal Year:
2021,
Volume and Issue:
8(14)
Published: May 16, 2021
Abstract
Gene
therapy
provides
a
promising
strategy
for
curing
monogenetic
disorders
and
complex
diseases.
However,
there
are
challenges
associated
with
the
use
of
viral
delivery
vectors.
The
advent
nanomedicine
represents
quantum
leap
in
application
gene
therapy.
Recent
advances
stimulus‐responsive
nonviral
nanocarriers
indicate
that
they
efficient
systems
loading
unloading
therapeutic
nucleic
acids.
Some
responsive
to
cues
derived
from
internal
environment,
such
as
changes
pH,
redox
potential,
enzyme
activity,
reactive
oxygen
species,
adenosine
triphosphate,
hypoxia.
Others
external
stimulations,
including
temperature
gradients,
light
irradiation,
ultrasonic
energy,
magnetic
field.
Multiple
stimuli‐responsive
strategies
have
also
been
investigated
recently
experimental
Small,
Journal Year:
2021,
Volume and Issue:
18(6)
Published: Dec. 22, 2021
Abstract
Multiple
biological
barriers
must
be
considered
in
the
design
of
nanomedicines,
including
prolonged
blood
circulation,
efficient
accumulation
at
target
site,
effective
penetration
into
tissue,
selective
uptake
nanoparticles
cells,
and
successful
endosomal
escape.
However,
different
particle
sizes,
surface
chemistries,
sometimes
shapes
are
required
to
achieve
desired
transport
properties
each
step
delivery
process.
In
response,
this
review
highlights
recent
developments
switchable
whose
size,
chemistry,
shape,
or
a
combination
thereof
can
altered
as
function
time,
disease‐specific
microenvironment,
and/or
via
an
externally
applied
stimulus
enable
improved
optimization
nanoparticle
The
practical
use
such
chemotherapy,
bioimaging,
photothermal
therapy,
other
applications
is
also
discussed.
Journal of Medicinal Chemistry,
Journal Year:
2022,
Volume and Issue:
65(6), P. 5057 - 5071
Published: Feb. 17, 2022
The
catalytic
properties
of
proteolysis
targeting
chimeras
(PROTACs)
may
lead
to
uncontrolled
off-tissue
target
degradation
that
causes
potential
toxicity,
limiting
their
clinical
applications.
precise
control
this
technology
in
a
tissue-selective
manner
can
minimize
the
toxicity.
Hypoxia
is
hallmark
most
solid
tumors,
accompanied
by
elevated
levels
nitroreductase
(NTR).
Based
on
character,
we
presented
type
NTR-responsive
PROTACs
selectively
degrade
proteins
interest
(POI)
tumor
tissues.
Compound
17-1
was
first
PROTAC
synthesized
incorporating
caging
group
Von
Hippel–Lindau
(VHL)
E3
ubiquitin
ligase
ligand.
It
could
be
activated
NTR
release
active
17
efficiently
EGFR
protein
and
subsequently
exert
antitumor
efficacy.
Thus,
general
strategy
for
induce
POI
tissues
established,
which
provided
generalizable
platform
development
NTR-controlled
achieve
selective
degradation.
