Analytical Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 3, 2025
DNAzymes,
known
for
their
programmability,
stability,
and
cost-effectiveness,
are
powerful
tools
signal
transduction
in
complex
biological
systems.
However,
application
responding
to
target
effectors
is
often
hindered
by
limited
catalytic
efficiency
susceptibility
unintended
activation.
Here
we
propose
an
allosteric
cooperative
activation
strategy
program
a
split
DNAzyme
modulator
(STATER)
that
enables
sensitive
accurate
electrochemiluminescence
(ECL)
biosensing
of
interleukin-6
(IL-6)
mRNA.
Our
design
features
STATER
leverages
DNA
tetrahedron
as
central
scaffold,
equipped
with
two
pairs
T-shaped
hairpin
probes
(TP)
helper
(HP).
Specifically,
the
TP
contains
apurinic/apyrimidinic
endonuclease
1
(APE1)
recognition
sites,
IL-6
mRNA
region,
partzyme
fragment,
while
HP
corresponding
paired
fragment.
Unlike
conventional
modulators
rely
on
single
effector
activation,
integrates
mechanism,
which
ensures
all
preblocked
components
synergistically
activated
assembled
within
confined
space,
facilitating
rapid
specific
reconstruction
DNAzyme's
active
domain.
Furthermore,
upon
APE1
mRNA,
inactive
partzymes
undergo
assembly
via
toehold
exchange
displacement
reaction,
switching
cleavage
reactivity
STATER.
This
mechanism
establishment
threshold
thereby
minimizing
nonspecific
scenarios.
studies
demonstrate
exhibits
outstanding
sensitivity
selectivity
detection
using
supramolecular
gold
nanoclusters
network-based
ECL
platform.
The
biosensor
provides
linear
span
from
×
10–13
10–7
M,
limit
low
3.26
10–14
highlighting
STATER's
potential
detecting
various
analytes
Neutrophil-derived
extracellular
vesicles
(NEVs)
are
critically
involved
in
disease
progression
and
considered
potential
biomarkers.
However,
the
tedious
processes
of
NEV
separation
detection
restrain
their
use.
Herein,
we
presented
an
integrated
microfluidic
chip
for
(IMCN)
analysis,
which
achieved
immune-separation
CD66b+
NEVs
multiplexed
contained
miRNAs
(termed
signatures)
by
using
10
μL
serum
samples.
The
optimized
microchannel
flow
rate
IMCN
enabled
efficient
capture
(>90%).
After
recognition
captured
a
specific
CD63
aptamer,
on-chip
rolling
circle
amplification
(RCA)
reaction
was
triggered
released
aptamers
from
heat-lysed
NEVs.
Then,
RCA
products
bound
to
molecular
beacons
(MBs),
initiating
allosteric
hairpin
structures
amplified
"turn
on"
fluorescence
signals
(RCA-MB
assay).
Clinical
sample
analysis
showed
that
signatures
had
high
area
under
curve
(AUC)
distinguishing
between
healthy
control
(HC)
gastric
cancer
(GC)
(0.891),
benign
diseases
(BGD)
GC
(0.857).
Notably,
AUC
reached
0.912
with
combination
five
biomarkers
(NEV
signatures,
CEA,
CA199)
differentiate
HC,
diagnostic
accuracy
further
increased
machine
learning
(ML)-based
ensemble
classification
system.
Therefore,
developed
is
valuable
platform
may
have
use
diagnosis.
International Journal of Nanomedicine,
Год журнала:
2024,
Номер
Volume 19, С. 8211 - 8236
Опубликована: Авг. 1, 2024
Hypoxia,
as
a
prominent
feature
of
the
tumor
microenvironment,
has
profound
impact
on
multicomponent
changes
within
this
environment.
Under
hypoxic
conditions,
malignant
phenotype
cells,
variety
cell
types
well
intercellular
communication
and
material
exchange,
undergo
complex
alterations.
These
provide
significant
prospects
for
exploring
mechanisms
development
under
different
microenvironmental
conditions
devising
therapeutic
strategies.
Exosomes
secreted
by
cells
stromal
are
integral
components
serving
crucial
mediators
have
consequently
garnered
increasing
attention
from
researchers.
This
review
focuses
which
promote
release
exosomes
alter
their
encapsulated
contents.
It
also
examines
effects
derived
immune
other
microenvironment.
Additionally,
we
summarize
current
research
progress
potential
clinical
applications
propose
future
directions
in
field.
Advanced Science,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 23, 2024
Gastric
cancer
(GC)
is
recognized
as
the
fifth
most
prevalent
malignant
tumor
worldwide.
It
characterized
by
diverse
clinical
symptoms,
treatment
responses,
and
prognoses.
In
GC
prognosis,
promotion
of
epithelial-mesenchymal
transition
(EMT)
fosters
cell
invasion
metastasis,
thereby
triggering
dissemination
cells.
This
study
proposes
a
nucleic
acid
amplification
circuit-based
hydrogel
(NACH)
assay
for
identifying
exosomal
miRNA
derived
from
metastatic
GC.
The
NACH
employs
rolling
circle
method
targets
miRNA-21,
tumor-related
oncogene,
miRNA-99a,
which
promotes
EMT.
Specific
probes
each
target
are
immobilized
within
hydrogel,
enabling
streamlined,
one-step
reaction.
exhibits
detection
limit
1
fm
miRNA-21
rapid
highly
sensitive
on-site
detection.
Performance
evaluation
using
extracted
culture
media,
mouse
plasma,
human
plasma
revealed
fluorescence
intensity
patterns
similar
to
those
obtained
in
qRT-PCR.
Furthermore,
deploying
custom-developed
portable
fluorometer
allows
diagnostic
performance
assessment
point-of-care
testing
samples
patients.
These
findings
emphasize
potential
be
used
robust
tool
genetic
diagnosis
based
on
exosome
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
Analytical Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
Herein,
a
supramolecular
DNA
nanodevice
was
formed
via
the
rolling
circle
amplification
(RCA)
and
hybridization
chain
reaction
(HCR)
cascade
on
tetrahedral
nanostructure
(TDN)
to
achieve
simultaneous
sensitive
detection
intracellular
imaging
of
dual-miRNAs
related
liver
cancer.
The
effectively
addressed
limitations
low
probe
loading
capacity
in
traditional
TDN
nanodevices
by
enriching
plenty
signal
probes
around
single
TDN,
significantly
enhancing
fluorescence
signal.
Impressively,
with
fulcrum
dense
structure
imparted
strong
rigidity,
ensuring
stability
decrease
aggregation
quenching
for
further
increasing
response.
Consequently,
biosensor
based
enabled
miRNA221
miRNA222,
achieved
accurate
situ
displaying
improved
capabilities
compared
TDN-based
nanodevices.
More
importantly,
precise
miRNA222
could
distinguish
hepatocellular
carcinoma
cells
different
degrees
metastasis
from
human
normal
cells,
providing
more
information
diagnosis
development
carcinoma.
Analytical Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 5, 2025
CRISPR/Cas
systems
have
emerged
as
promising
tools
for
nucleic
acid
detection.
However,
their
practical
applications
been
limited
by
poor
specificity
and
the
need
additional
preprocessing
steps.
Inspired
concept
of
transformers,
we
found
that
changing
forms
crRNA
with
spatial
arrangement
may
endow
an
enhanced
performance
Specifically,
rationally
designed
two
transformers─swap
split
crRNA─and
they
direct
system
cis-
trans-
cleavage
decreased
Cas
binding
affinity
possess
both
DNA
RNA
detection
abilities.
Based
on
these
findings,
our
strategy
enabled
identification
clinical
prostatic
cancer
in
a
one-step
reaction,
remarkable
sensitivity
90.0%
96.0%.
Our
study
deepens
understanding
introduces
simple
specificity,
sensitivity,
functionality
molecular
diagnosis.
Analytical Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 3, 2024
Lung
cancer
(LC)
is
the
leading
cause
of
cancer-related
mortality
worldwide,
underscoring
an
urgent
need
for
strategies
that
enable
early
detection
and
phenotypic
classification.
Here,
we
conducted
a
label-free
surface-enhanced
Raman
spectroscopic
(SERS)
analysis
serum
exosomes
from
643
participants
to
elucidate
biochemical
deregulation
associated
with
LC
progression
unique
phenotypes
different
subtypes.
Iodide-modified
silver
nanofilms
were
prepared
rapidly
acquire
SERS
spectra
high
signal-to-noise
ratio
using
0.5
μL
patient
exosomes.
We
performed
interpretable
automated
machine
learning
(ML)
differential
features
build
diagnostic
models,
which
achieved
accuracies
100%
81%
stage
I
lung
adenocarcinoma
its
preneoplasia,
respectively.
In
addition,
ML-derived
exosomal
models
effectively
recognized
subtypes
disease
stages
guide
precision
treatment.
Our
findings
demonstrate
spectral
fingerprinting
circulating
holds
promise
decoding
clinical
status
LC,
thus
aiding
in
improving
management
patients.