Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 9, 2024
Abstract
Proteolysis‐targeting
chimeras
(PROTACs)
have
accelerated
drug
development;
however,
some
challenges
still
exist
owing
to
their
lack
of
tumor
selectivity
and
on‐demand
protein
degradation.
Here,
we
developed
a
miR
NA‐
i
nitiated
ssembled
pre‐PRO
TAC
(miRiaTAC)
platform
that
enables
the
activation
termination
target
degradation
in
cell
type‐specific
manner.
Using
miRNA‐21
as
model,
engineered
DNA
hairpins
labeled
with
JQ‐1
pomalidomide
facilitated
modular
assembly
DNA‐encoded
pre‐PROTACs
through
hybridization
chain
reaction.
This
configuration
promoted
selective
polyubiquitination
BRD4
upon
miR‐21
initiation,
highlighting
significant
minimal
systemic
toxicity.
Furthermore,
incorporates
photolabile
groups,
enabling
precise
optical
control
during
assembly/disassembly,
mitigating
risk
excessive
Additionally,
by
introducing
secondary
ligand
targeting
CDK6,
these
were
used
scaffold
for
programmable
active
miRiaTACs
containing
two
different
warheads
exact
stoichiometry,
orthogonal
multitarget
The
integration
near‐infrared
light‐mediated
photodynamic
therapy
an
upconversion
nanosystem
further
enhanced
efficacy
potent
vivo
anticancer
activity.
We
anticipate
miRiaTAC
represents
intersection
between
dynamic
nanotechnology
PROTAC,
potentially
expanding
versatility
PROTAC
toolkit
cancer
therapy.
Biomacromolecules,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 11, 2024
Glioblastoma
multiforme
(GBM)
is
a
highly
malignant
brain
tumor
with
poor
prognosis
and
limited
treatment
options.
Drug
delivery
by
stimuli-responsive
nanocarriers
holds
great
promise
for
improving
the
modalities
of
GBM.
At
beginning
review,
we
highlighted
stimuli-active
polymeric
carrying
therapies
that
potentially
boost
anti-GBM
responses
employing
endogenous
(pH,
redox,
hypoxia,
enzyme)
or
exogenous
stimuli
(light,
ultrasonic,
magnetic,
temperature,
radiation)
as
triggers
controlled
drug
release
mainly
via
hydrophobic/hydrophilic
transition,
degradability,
ionizability,
etc.
Modifying
these
target
ligands
further
enhanced
their
capacity
to
traverse
blood-brain
barrier
(BBB)
preferentially
accumulate
in
glioma
cells.
These
unique
features
lead
more
effective
cancer
minimal
adverse
reactions
superior
therapeutic
outcomes.
Finally,
review
summarizes
existing
difficulties
future
prospects
treating
Overall,
this
offers
theoretical
guidelines
developing
intelligent
versatile
facilitate
precise
GBM
clinical
settings.
Chemical Society Reviews,
Journal Year:
2024,
Volume and Issue:
53(19), P. 9582 - 9608
Published: Jan. 1, 2024
Targeted
protein
degradation
(TPD)
has
emerged
as
a
revolutionary
paradigm
in
drug
discovery
and
development,
offering
promising
avenue
to
tackle
challenging
therapeutic
targets.
Unlike
traditional
approaches
that
focus
on
inhibiting
function,
TPD
aims
eliminate
proteins
of
interest
(POIs)
using
modular
chimeric
structures.
This
is
achieved
through
the
utilization
proteolysis-targeting
chimeras
(PROTACs),
which
redirect
POIs
E3
ubiquitin
ligases,
rendering
them
for
by
cellular
ubiquitin-proteasome
system
(UPS).
Additionally,
other
technologies
such
lysosome-targeting
(LYTACs)
autophagy-based
degraders
facilitate
transportation
endo-lysosomal
or
autophagy-lysosomal
pathways
degradation,
respectively.
Despite
significant
growth
preclinical
research,
many
fail
progress
beyond
this
stage
development.
Various
factors
contribute
limited
success
agents,
including
hurdle
inadequate
delivery
target
site.
Integrating
into
platforms
could
surmount
challenges
Macromolecular Rapid Communications,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 7, 2025
Spatial
control
over
supramolecular
self-assembly
prevails
in
living
system,
yet
remains
difficult
to
replicate
synthetic
scenarios.
Here,
on
the
basis
of
a
hydrazone
formation-mediated
hydrogelation
access
patterning
hydrogels
is
demonstrated
via
light-triggered
catalysis
strategy.
A
photoacid
generator
that
can
produce
protons
aqueous
solutions
upon
irradiation
employed.
The
generated
lead
drop
pH
around
three
units
(initial
7.0),
effectively
accelerating
formation
and
gelators.
Because
catalysis,
samples
presence
show
lower
critical
gelation
concentration,
higher
stiffness,
denser
networks.
Importantly,
by
performing
selective
using
differently
shaped
masks,
various
spatially
resolved
following
shapes
masks
are
fabricated.
concept
realize
spatial
provides
an
alternative
approach
toward
bottom-up
fabrication
structured
soft
materials
for
applications
such
as
tissue
engineering,
single
cell
manipulation,
biosensing.
Nano Letters,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 27, 2025
Protein
carboxyl
methyltransferase
(PCMT)
restores
aspartate
isomers
in
proteins
and
plays
a
critical
role
cancer
prognosis.
However,
vivo
detection
of
PCMT
remains
challenging.
Here,
we
report
the
isomerization-regulated
situ
assembly
peptides
into
supramolecular
probes
within
living
cells
for
bladder
cancer.
The
peptide
consists
alternating
hydrophobic
hydrophilic
residues
contains
an
isoAsp
residue
as
kinked
site
to
prevent
facial
amphiphilicity
peptide.
Exposure
converts
Asp
peptide,
thereby
promoting
its
nanofibers.
Incorporation
7-nitro-2,1,3-benzoxadiazole
(NBD)
nanofibers
enables
based
on
hydrophobicity-dependent
fluorescence
NBD
units.
Both
cellular
animal
studies
confirm
capability
efficient
PCMT.
Our
finding
demonstrates
strategy
regulating
systems
thus
provides
new
tool
creation
biomedical
agents
future.
Macromolecular Bioscience,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 22, 2025
Abstract
In
addition
to
the
20
standard
amino
acids
that
form
building
blocks
of
proteins,
nature
employs
alternative
create
specialized
“noncanonical
peptides.”
These
unique
peptides,
found
in
organisms
from
bacteria
humans,
often
exhibit
unconventional
structures
and
functionalities,
playing
critical
roles
modulating
cellular
processes,
particularly
as
antibiotics.
Their
potential
has
attracted
significant
interest
for
designing
novel
functional
materials
based
on
noncanonical
peptides.
This
review
highlights
recent
advances
generation
application
peptide
assemblies.
It
begins
with
a
definition
including
classic
examples
showcase
their
distinct
useful
biological
activities.
Then
applications
assemblies
developing
anticancer
therapeutics
are
discussed,
focusing
representative
studies
demonstrate
efficacy
versatility
targeting
tumor
cells.
Beyond
oncology,
it
is
explored
how
have
been
utilized
biomaterials,
regenerative
medicine,
molecular
imaging
catalysis.
Finally,
perspectives
offered
future
directions
this
rapidly
evolving
field,
emphasizing
exciting
opportunities
remaining
challenges
will
drive
continued
innovation
applying
peptide‐based
Science and Technology of Advanced Materials,
Journal Year:
2024,
Volume and Issue:
25(1)
Published: June 28, 2024
Nanoarchitectonics,
as
a
technology
to
arrange
nano-sized
structural
units
such
molecules
in
desired
configuration,
requires
nano-organization,
which
usually
relies
on
intermolecular
interactions.
This
review
briefly
introduces
the
development
of
using
enzymatic
reactions
control
interactions
for
generating
artificial
nanoarchitectures
cellular
environment.
We
begin
discussion
with
early
examples
and
uniqueness
enzymatically
controlled
self-assembly.
Then,
we
describe
intracellular
nanostructures
their
relevant
applications.
Subsequently,
discuss
cases
forming
cell
surface
via
reactions.
Following
that,
highlight
use
creating
intercellular
nanostructures.
Finally,
provide
summary
outlook
promises
future
direction
this
strategy.
Our
aim
is
give
an
updated
introduction
reaction
regulating
interactions,
phenomenon
ubiquitous
biology
but
relatively
less
explored
by
chemists
materials
scientists.
goal
stimulate
new
developments
simple
versatile
approach
addressing
societal
needs.
