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.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(15), P. 10753 - 10766
Published: April 5, 2024
Proteolysis
targeting
chimera
(PROTAC)
technology
is
an
innovative
strategy
for
cancer
therapy,
which,
however,
suffers
from
poor
delivery
and
limited
capability
protein
of
interest
(POI)
degradation.
Here,
we
report
a
the
in
situ
formulation
antineoplastic
Supra-PROTACs
via
intracellular
sulfatase-responsive
assembly
peptides.
Coassembling
sulfated
peptide
with
two
ligands
binding
to
ubiquitin
VHL
Bcl-xL
leads
formation
pro-Supra-PROTAC,
which
ratio
rationally
optimized
based
on
their
affinity.
The
resulting
pro-Supra-PROTAC
precisely
undergoes
enzyme-responsive
into
nanofibrous
cells
overexpressing
sulfatase.
Mechanistic
studies
reveal
that
pro-Supra-PROTACs
selectively
cause
apparent
cytotoxicity
through
degradation
activation
caspase-dependent
apoptosis,
during
ligand
improves
bioactivity
POI
cell
death.
In
vivo
show
enhanced
tumor
accumulation
retention
pro-Supra-PROTACs,
as
well
inhibiting
growth
excellent
biosafety
when
coadministrating
chemodrugs.
Our
findings
provide
new
approach
enzyme-regulated
peptides
living
development
PROTACs
high
delivering
efficiency.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(19), P. 12901 - 12906
Published: May 3, 2024
Cholesterol-rich
membranes
play
a
pivotal
role
in
cancer
initiation
and
progression,
necessitating
innovative
approaches
to
target
these
for
inhibition.
Here
we
report
the
first
case
of
unnatural
peptide
(1)
assemblies
capable
depleting
cholesterol
inhibiting
cells.
Peptide
1
self-assembles
into
micelles
is
rapidly
taken
up
by
cells,
especially
when
combined
with
an
acute
cholesterol-depleting
agent
(MβCD).
Click
chemistry
has
confirmed
that
depletes
cell
membrane
cholesterol.
It
localizes
membrane-rich
organelles,
including
endoplasmic
reticulum,
Golgi
apparatus,
lysosomes.
Furthermore,
potently
inhibits
malignant
working
synergistically
cholesterol-lowering
agents.
Control
experiments
have
C-terminal
capping
amino
acid
residues
(i.e.,
BiP)
are
essential
both
depletion
potent
This
work
highlights
as
promising
platform
targeting
controlling
fates.
Advanced NanoBiomed Research,
Journal Year:
2024,
Volume and Issue:
4(4)
Published: Feb. 6, 2024
Intracellular
assemblies
play
vital
roles
in
maintaining
cellular
functions
through
structural
recognition‐mediated
interactions.
The
introduction
of
artificial
structures
has
garnered
substantial
interest
modulating
via
activation/inhibition
interactions
with
biomacromolecules.
However,
the
uptake
these
high‐molecular‐weight
may
limit
their
performance.
Recently,
intracellular
chemical‐reaction‐induced
self‐assembly
emerged
as
a
promising
strategy
for
generating
situ
nanostructures
biofunctionalities
interacting
This
approach
addresses
challenge
synthetic
reactions
occurring
complex
environments
by
utilizing
diverse
chemical
that
respond
to
endogenous
and
exogenous
stimuli.
review
provides
an
overview
latest
advancements
techniques.
It
focuses
on
responsiveness
specific
conditions,
such
redox
overexpressed
enzymes.
Additionally,
initiation
stimuli,
including
reagents
irradiation
is
explored.
Polymerization‐induced
hydrophobicity
highlighted,
leading
into
micro‐/nanostructures.
These
processes
contribute
construction
materials
morphologies,
offering
versatile
functionalities
biological
applications.
Advanced Science,
Journal Year:
2023,
Volume and Issue:
11(8)
Published: Sept. 7, 2023
Abstract
The
term
“in
vivo
(“in
the
living”)
chemistry”
refers
to
chemical
reactions
that
take
place
in
a
complex
living
system
such
as
cells,
tissue,
body
liquids,
or
even
an
entire
organism.
In
contrast,
occur
generally
outside
organisms
artificial
environment
(e.g.,
test
tube)
are
referred
vitro.
Over
past
decades,
significant
contributions
have
been
made
this
rapidly
growing
field
of
chemistry,
but
it
is
still
not
fully
understood,
which
transformations
proceed
efficiently
without
formation
by‐products
how
product
environments
can
be
characterized.
Potential
applications
imagined
synthesize
drug
molecules
directly
within
cell
confer
new
cellular
functions
through
controlled
will
improve
understanding
systems
and
develop
therapeutic
strategies.
guiding
principles
contribution
twofold:
1)
Which
translated
from
laboratory
system?
2)
characterization
methods
suitable
for
studying
structure
environments?
Journal of the American Chemical Society,
Journal Year:
2023,
Volume and Issue:
146(1), P. 330 - 341
Published: Dec. 19, 2023
Implementing
dissipative
assembly
in
living
systems
is
meaningful
for
creation
of
materials
or
even
artificial
life.
However,
intracellular
remains
scarce
and
significantly
impeded
by
the
challenges
lying
precisely
operating
chemical
reaction
cycles
under
complex
physiological
conditions.
Here,
we
develop
organelle-mediated
self-assembly
peptides
cells
fueled
GSH,
via
design
a
mitochondrion-targeting
redox-responsive
hexapeptide.
While
hexapeptide
undergoes
efficient
self-assembly,
addition
GSH
into
peptide
solution
presence
mitochondrion-biomimetic
liposomes
containing
hydrogen
peroxide
allows
transient
peptides.
Internalization
LPS-stimulated
macrophages
leads
to
driven
reduction
association
assemblies
with
mitochondria.
The
facilitates
reversible
oxidation
reduced
mitochondrion-residing
ROS
thereby
dissociates
from
mitochondria
re-enter
cytoplasm
reduction.
metastable
peptide–mitochondrion
complexes
prevent
thermodynamically
equilibrated
thus
establishing
stimulated
macrophages.
entire
self-assembling
process
elimination
elevated
decrease
pro-inflammatory
cytokine
expression.
Creating
assisted
internal
structures
provides
new
avenues
development
medical
agents
future.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(45)
Published: July 24, 2024
Abstract
The
strategy
of
in
vivo
self‐assembly
has
been
developed
for
improved
enrichment
and
long‐term
retention
anticancer
drug
tumor
tissues.
However,
most
self‐assemblies
with
non‐covalent
bonding
interactions
are
susceptible
to
complex
physiological
environments,
leading
weak
stability
loss
biological
function.
Here,
we
develop
a
coupling‐induced
assembly
(CIA)
generate
covalently
crosslinked
nanofibers,
which
is
applied
situ
constructing
artificial
shell
on
mitochondria.
oxidation‐responsive
peptide‐porphyrin
conjugate
P1
synthesized,
self‐assemble
into
nanoparticles.
Under
the
oxidative
microenvironment
mitochondria,
coupling
thiols
causes
formation
dimers,
further
ordered
stacked
nanofibers.
As
result,
constructed
mitochondria
efficiently
through
multivalent
cooperative
due
increased
binding
sites.
ultrasound
(US)
irradiation,
porphyrin
molecules
produce
large
amount
reactive
oxygen
species
(ROS)
that
act
adjacent
mitochondrial
membrane,
exhibiting
~2‐fold
higher
antitumor
activity
than
nanoparticles
vitro
vivo.
Therefore,
mitochondria‐targeted
CIA
provides
novel
perspective
sonodynamic
therapy
(SDT)
shows
potential
applications
therapies.
