Chemical Communications,
Год журнала:
2024,
Номер
60(37), С. 4942 - 4945
Опубликована: Янв. 1, 2024
The
triple-mode
nanosensor
platform
developed
in
this
work
utilizes
fluorescence
anisotropy
and
Förster
resonance
energy
transfer
strategies,
exhibiting
high
detection
capabilities
DNA
microRNA
analysis.
ACS Synthetic Biology,
Год журнала:
2025,
Номер
14(1), С. 21 - 40
Опубликована: Янв. 6, 2025
The
field
of
healthcare
diagnostics
is
navigating
complex
challenges
driven
by
evolving
patient
demographics
and
the
rapid
advancement
new
technologies
worldwide.
In
response
to
these
challenges,
biosensors
offer
distinctive
advantages
over
traditional
diagnostic
methods,
such
as
cost-effectiveness,
enhanced
specificity,
adaptability,
making
their
integration
with
point-of-care
(POC)
platforms
more
feasible.
recent
years,
aptasensors
have
significantly
evolved
in
capabilities
through
emerging
microfluidics,
Clustered
Regularly
Interspaced
Short
Palindromic
Repeats
(CRISPR)
systems,
wearable
devices,
machine
learning
(ML),
driving
progress
precision
medicine
global
solutions.
Moreover,
advancements
not
only
improve
accuracy
but
also
hold
potential
revolutionize
early
detection,
reduce
costs,
outcomes,
especially
resource-limited
settings.
This
Account
examines
key
advancements,
focusing
on
how
scientific
breakthroughs,
including
artificial
intelligence
(AI),
improved
sensitivity
precision.
Additionally,
has
enabled
real-time
monitoring
data
analysis,
fostering
advances
personalized
healthcare.
Furthermore,
commercialization
aptasensor
could
increase
availability
clinical
settings
support
use
widespread
solutions
for
health
challenges.
Hence,
this
review
discusses
technological
improvements,
practical
uses,
prospects
while
surrounding
standardization,
validation,
interdisciplinary
collaboration
application.
Finally,
ongoing
efforts
address
are
ensure
that
can
be
effectively
implemented
diverse
systems.
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.
Nucleic Acids Research,
Год журнала:
2025,
Номер
53(3)
Опубликована: Янв. 24, 2025
Abstract
The
flexibility
and
programmability
of
CRISPR–Cas
technology
have
made
it
one
the
most
popular
tools
for
biomarker
diagnostics
gene
regulation.
Especially,
CRISPR–Cas12
system
has
shown
exceptional
clinical
diagnosis
editing
capabilities.
Here,
we
discovered
that
although
top
loop
5′
handle
guide
RNA
can
undergo
central
splitting,
deactivating
CRISPR–Cas12a,
segments
dramatically
restore
CRISPR
function
through
nucleic
acid
self-assembly
or
interactions
with
small
molecules
aptamers.
This
discovery
forms
basis
an
engineered
Cas12a
a
programmable
proximity-activated
(PARC–Cas12a)
links
targets
interest
to
dsDNA.
Leveraging
efficient
trans-
cis-cleavage
Cas12,
our
findings
further
inspired
detection
platform
design
RNAs
non-nucleic
biomarkers,
enabling
highly
sensitive
multiplexed
analysis.
We
demonstrated
feasibility
RNA-controllable
knockout/knockdown
in
Escherichia
coli.
Notably,
successfully
validated
regulatory
capabilities
PARC–Cas12a
within
mammalian
cell
systems
by
utilizing
classical
theophylline
molecule–aptamer
system.
Our
results
introduce
toolbox
precise
regulation,
allowing
development
versatile
diagnostic
tools,
complex
synthetic
biological
circuits,
cellular
biosensors.
Late-stage
diagnosis
is
a
major
contributor
to
cancer
mortality
and
thus
leads
increased
fatality,
making
early
detection
crucial
for
improving
survival
rates.
Circulating
tumor
cells
(CTC),
detectable
before
primary
tumors
become
clinically
apparent,
have
emerged
as
vital
biomarkers
the
identification
of
aggressive
cancers.
Here,
develop
single-atom
nanozyme
integrated
nanoarray
3D
nano-biointerface
ultrasensitive
electrochemical
screening
CTCs
from
hepatocellular
carcinoma.
This
cytosensor
capable
identifying
CTC
at
single-cell
level,
achieving
an
impressive
area
under
curve
0.96
in
receiver
operating
characteristics,
comparable
simulated
multi-indicator
diagnostic
strategies.
strategy
shows
great
potential
non-invasive
carcinoma
promising
be
applied
universally
diagnosis.
ACS Synthetic Biology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 29, 2025
Advancements
in
molecular
diagnostics,
such
as
polymerase
chain
reaction
and
next-generation
sequencing,
have
revolutionized
disease
management
prognosis.
Despite
these
advancements
the
field
faces
challenges
due
to
high
operational
costs
need
for
sophisticated
equipment
highly
trained
personnel
besides
having
several
technical
limitations.
The
emergent
of
CRISPR/Cas
sensing
technology
is
showing
promise
a
new
paradigm
clinical
although
widespread
adoption
remains
limited.
This
perspective
paper
discusses
specific
cases
where
can
surmount
existing
diagnostic
methods
by
stressing
significant
role
that
play
revolutionizing
diagnostics.
It
underscores
urgency
importance
addressing
technological
regulatory
hurdles
must
be
overcome
harness
this
effectively
laboratories.
Analytical Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 11, 2025
The
low
abundance,
complex
phenotypes,
and
need
for
sophisticated
blood
preprocessing
pose
substantial
obstacles
to
the
clinical
implementation
of
circulating
tumor
cells
(CTCs).
Herein,
we
constructed
a
cascaded
PMMA
chip-based
platform
separation
CTCs
from
other
within
samples,
as
well
distinguishing
detection
epithelial
mesenchymal
CTCs.
primary
physical
chip
(PS-Chip)
focused
sorted
whole
via
Dean
flow
fractionation
(DFF)
according
size
differences
between
cells,
being
capable
eliminating
approximately
93.7%
red
(RBCs)
68.4%
white
(WBCs)
while
maintaining
CTC
recovery
rate
around
90%.
Subsequently,
further
purify
isolated
in
upstream,
partitioned
immunoaffinity
capture
(PICD-Chip)
featuring
with
two
independent
chambers
(Zone
1,
Zone
2)
was
designed,
each
which
premodified
Gel-GO/E/V-Apt
complexes
that
specifically
recognize
distinct
enabling
residual
upstream
isolation.
Upon
subsequent
introduction
probes,
namely
EpCAM
vimentin
aptamer-modified
mesoporous
Pt
nanoparticles
(mPtNPs/E/V-Apt),
into
1
2,
respectively,
heterogeneous
ranging
5
200/mL
captured
were
distinguished
quantified
utilizing
exceptional
peroxidase
activity
mPtNPs.
integrated
approach
efficient
enrichment
differentiation
phenotypic
under
requirement
high
purity
has
enabled
successful
application
diagnosis
colon
cancer
patients
at
different
stages.
Biological
barriers
significantly
impede
the
delivery
of
nanotherapeutics
to
diseased
tissues,
diminishing
therapeutic
efficacy
across
pathologies
such
as
cancer
and
inflammatory
disorders.
Although
conventional
strategies
integrate
multifunctional
designs
molecular
components
into
nanomaterials
(NMs),
many
approaches
remain
insufficient
overcome
these
barriers.
Key
challenges,
including
inadequate
drug
accumulation
at
target
sites
nonspecific
biodistribution,
persist
in
nanotherapeutic
development.
NMs,
which
harness
ability
precisely
modulate
spatiotemporally
control
release
kinetics,
represent
a
transformative
platform
for
targeted
therapy.
In
this
review,
we
highlight
biological
obstacles
limiting
effective
treatment
evaluate
how
stimuli-responsive
NMs
address
constraints.
By
leveraging
exogenous
endogenous
stimuli,
improve
specificity,
reduce
off-target
effects,
amplify
activity
within
pathological
microenvironments.
We
systematically
analyze
rational
design
synthesis
driven
by
advances
oncology,
biomaterials
science,
nanoscale
engineering.
Furthermore,
NM
classes-including
polymeric,
lipid-based,
inorganic,
hybrid
systems
explore
functionalization
using
targeting
ligands,
antibodies,
biomimetic
coatings.
Diverse
are
evaluated,
small-molecule
prodrug
activation,
peptide-
protein-based
targeting,
nucleic
acid
payloads,
engineered
cell-mediated
transport.
Despite
promise
challenges
biocompatibility,
scalable
fabrication,
clinical
translation
must
be
addressed.
elucidating
structure-function
relationships
refining
stimulus-triggered
mechanisms,
pave
way
precision
oncology
strategies,
enabling
patient-specific
therapies
with
enhanced
safety.
This
interdisciplinary
insights
aims
catalyze
innovation
next-generation
nanomedicine
treatment.