Programmable DNA Nanoswitch-Regulated Plasmonic CRISPR/Cas12a-Gold Nanostars Reporter Platform for Nucleic Acid and Non-Nucleic Acid Biomarker Analysis Assisted by a Spatial Confinement Effect
Nano Letters,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 15, 2025
CRISPR/Cas
12a
system
based
nucleic
acid
and
non-nucleic
targets
detection
faces
two
challenges
including
(1)
multiple
crRNAs
are
needed
for
biomarkers
(2)
insufficient
sensitivity
resulted
from
photobleaching
of
fluorescent
dyes
the
low
kinetic
cleavage
rate
a
traditional
single-strand
(ssDNA)
reporter.
To
address
these
limitations,
we
developed
programmable
DNA
nanoswitch
(NS)-regulated
plasmonic
CRISPR/Cas12a-gold
nanostars
(Au
NSTs)
reporter
platform
with
assistance
spatial
confinement
effect.
Through
simply
programming
target
recognition
sequence
in
NS,
only
one
crRNA
is
required
to
detect
both
biomarkers.
The
limit
decreased
by
∼196-fold
miRNA-375
122-fold
prostate-specific
antigen
(PSA),
respectively.
Moreover,
versatile
evaluation
PSA
clinical
urine
samples
can
also
be
achieved,
according
which
prostate
cancer
healthy
groups
well
identified.
Язык: Английский
Endogenous Enzyme-Activated Spatial Confinement DNA Nanowire with a Tumor Cell-Specific Response for High-Precision Imaging of the Tumor/Normal Cells Boundary
Analytical Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 12, 2025
Developing
tumor
cell-specific
imaging
approaches
is
essential
for
the
clear
delineation
of
margins.
However,
traditional
suffered
from
low
reaction
kinetics
as
well
limited
specificity
resulting
their
"always
active"
sensing
mode,
making
it
difficult
to
accurately
depict
boundary.
To
address
these
limitations,
we
developed
an
endogenous
enzyme-activated
spatial
confinement
DNA
nanowire
probe
(E-SCNW)
with
enhanced
tumor/normal
cell
discrimination
ratio
high
precision
cells
The
effect
can
improve
kinetics,
and
enzyme-activation
design
confine
fluorescence
response
region.
Additionally,
no
additional
delivery
carriers
were
required
during
cross
membrane
into
intracellular
space.
It
worth
noting
that
benefiting
design,
detection
limit
was
decreased
by
nearly
25.6-fold
4.46-fold
through
using
E-SCNW,
indicating
promising
prospects
in
high-precision
Язык: Английский
Engineering of a Multi‐Modular DNA Nanodevice for Spatioselective Imaging and Evaluation of NK Cell‐Mediated Cancer Immunotherapy
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 8, 2024
Granzyme
A
(GzmA)
secreted
by
natural
killer
(NK)
cells
has
garnered
considerable
interest
as
a
biomarker
to
evaluate
the
efficacy
of
cancer
immunotherapy.
However,
current
methodologies
selectively
monitor
spatial
distribution
GzmA
in
during
NK
cell-targeted
therapy
are
extremely
challenging,
primarily
due
existence
diverse
cell
populations,
low
levels
expression,
and
limited
availability
probes.
Herein
we
develop
multi-modular,
structurally-ordered
DNA
nanodevice
for
evaluating
cell-mediated
immunotherapy
(MODERN),
that
permits
spatioselective
imaging
through
GzmA-induced
apurinic/apyrimidinic
endonuclease
1
(APE1)
inactivation.
The
MODERN
incorporates
multiple
functional
modules,
including
an
APE1-gated
recognition
module,
photo-activated
amplification
aptamer-mediated
tumor-target
polycatenane
enabling
improved
sensitivity
specificity
towards
intracellular
GzmA.
was
activated
(on)
overexpression
APE1,
whereas
it
remained
silent
(off)
NK-treated
owing
APE1
Furthermore,
demonstrated
inactivation
blocks
cellular
repair
target
cells,
resulting
efficient
death.
This
relies
on
specific
should
be
beneficial
Язык: Английский
Engineering of a Multi‐Modular DNA Nanodevice for Spatioselective Imaging and Evaluation of NK Cell‐Mediated Cancer Immunotherapy
Angewandte Chemie,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 8, 2024
Abstract
Granzyme
A
(GzmA)
secreted
by
natural
killer
(NK)
cells
has
garnered
considerable
interest
as
a
biomarker
to
evaluate
the
efficacy
of
cancer
immunotherapy.
However,
current
methodologies
selectively
monitor
spatial
distribution
GzmA
in
during
NK
cell‐targeted
therapy
are
extremely
challenging,
primarily
due
existence
diverse
cell
populations,
low
levels
expression,
and
limited
availability
probes.
Herein
we
develop
m
ulti‐modular,
structurally‐
o
rdered
D
NA
nanodevice
for
e
valuating
cell‐mediated
cance
r
immu
n
otherapy
(MODERN),
that
permits
spatioselective
imaging
through
GzmA‐induced
apurinic/apyrimidinic
endonuclease
1
(APE1)
inactivation.
The
MODERN
incorporates
multiple
functional
modules,
including
an
APE1‐gated
recognition
module,
photo‐activated
amplification
aptamer‐mediated
tumor‐target
polycatenane
DNA
enabling
improved
sensitivity
specificity
towards
intracellular
GzmA.
was
activated
(on)
overexpression
APE1,
whereas
it
remained
silent
(off)
NK‐treated
owing
APE1
Furthermore,
demonstrated
inactivation
blocks
cellular
repair
target
cells,
resulting
efficient
death.
This
relies
on
specific
should
be
beneficial
evaluating
Язык: Английский
Fluorescence-Plane Polarization for the Real-Time Monitoring of Transferase Migration in Living Cells
Chemical Science,
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 1, 2024
Transferases
are
enzymes
that
exhibit
multisite
migration
characteristics.
Significantly,
enzyme
activity
undergoes
changes
during
this
process,
which
inevitably
impacts
the
physiological
function
of
living
organisms
and
can
even
lead
to
related
malignant
diseases.
However,
research
in
field
has
been
severely
hindered
by
lack
tools
for
simultaneous
differential
monitoring
site-specific
transferase
activity.
Herein,
we
propose
a
novel
strategy
integrates
fluorescence
signal
response
with
high
sensitivity
an
optical
rotation
superior
spatial
resolution.
To
validate
feasibility
strategy,
γ-glutamyltransferase
(GGT)
was
used
as
model
system
develop
dual-mode
chiral
probes
AC
Язык: Английский
Light-Triggered Plasmonic DNAzyme Walker Enables Precise Subcellular Molecular Imaging with Reduced Off-Mitochondria Signal Leakage
Analytical Chemistry,
Год журнала:
2024,
Номер
96(42), С. 16971 - 16977
Опубликована: Окт. 11, 2024
The
development
of
highly
sensitive
and
precise
imaging
techniques
capable
visualizing
crucial
molecules
at
the
subcellular
level
is
essential
for
elucidating
mitochondrial
functions
uncovering
novel
mechanisms
in
biological
processes.
However,
traditional
molecular
strategies
are
still
limited
by
off-mitochondria
signal
leakage
because
"always-active"
sensing
mode.
To
address
this
limitation,
we
have
developed
a
light-triggered
activation
sequence
activated
plasmonic
DNAzyme
walker
(PDW)
accurate
combination
an
organelle
localized
strategy,
upconversion
nanotechnology,
plasmon
enhanced
fluorescence
(PEF)
technique.
Exploiting
advantage
light
enables
control
over
when
where
to
activate
probe's
function,
effectively
reducing
as
validated
dynamic
monitoring
changes
signals
during
entry
process.
Furthermore,
leveraging
PEF
capability
triangular
gold
nanoprisms
(Au
NPRs),
intensity
can
be
approximately
11.9
times,
ensuring
imaging.
Язык: Английский