Frontiers in Oncology,
Год журнала:
2025,
Номер
15
Опубликована: Июнь 3, 2025
Background
Extracellular
vesicles
(EVs)
play
an
integral
role
in
cancer
biology,
influencing
tumor
progression,
metastasis,
and
microenvironment.
Due
to
their
distinctive
molecular
composition,
including
proteins,
nucleic
acids,
lipids,
EVs
present
a
promising
candidate
for
diagnostics
precision
therapeutics.
Methods
This
review
was
conducted
by
looking
up
recent
studies
obtained
through
PubMed,
Scopus,
Web
of
Science
databases
using
targeted
keywords
such
as
“Extracellular
Vesicles,”
“Cancer
Therapy,”
“Biomarkers,”
“Exosomes,”
“Tumor
Microenvironment,”
“Precision
Medicine.”
From
initial
4,320
articles
identified,
427
were
screened
after
applying
publication
filters,
resulting
the
inclusion
298
relevant
EV
isolation,
characterization,
diagnostic
sensitivity,
specificity,
therapeutic
efficacy.
Results
Biomarkers
derived
from
across
various
cancers
showed
high
performance.
For
example,
four
miRNA
showing
sensitivity
specificity
98%
96%
respectively
found
breast
cancer.
EV-RNA
surface
antigen
analyses
hepatocellular
carcinoma
with
93.8%
74.5%
specificity.
Additionally,
biomarker
colorectal
microRNA
miR-23a
miR-301a
had
89%
>70%
context
effective
drug
delivery
system
enhancing
chemotherapy
immunotherapy
reduced
systemic
toxicity.
Conclusion
The
theranostics
provide
great
capacity
early
diagnosis
personalized
treatment
based
on
Future
standardization
protocols
are
essential
translate
technologies
into
clinical
oncology.
Nanoscale,
Год журнала:
2024,
Номер
16(9), С. 4378 - 4391
Опубликована: Янв. 1, 2024
Schematic
illustration
of
the
combinational
strategy
nanotechnology
and
PROTACs
(Nano-PROTACs):
typical
shortcomings
traditional
nanotechnology-based
strategies
for
PROTAC
drugs
optimization.
JACS Au,
Год журнала:
2024,
Номер
4(2), С. 713 - 729
Опубликована: Фев. 12, 2024
Methylation
of
adenine
N6
(m6A)
is
the
most
frequent
RNA
modification.
On
mRNA,
it
catalyzed
by
METTL3–14
heterodimer
complex,
which
plays
a
key
role
in
acute
myeloid
leukemia
(AML)
and
other
types
blood
cancers
solid
tumors.
Here,
we
disclose
first
proteolysis
targeting
chimeras
(PROTACs)
for
an
epitranscriptomics
protein.
For
designing
PROTACs,
made
use
crystal
structure
complex
with
potent
selective
small-molecule
inhibitor
(called
UZH2).
The
optimization
linker
started
from
desfluoro
precursor
UZH2
whose
synthesis
more
efficient
than
that
UZH2.
nine
PROTAC
molecules
featured
PEG-
or
alkyl-based
linkers,
but
only
latter
showed
cell
penetration.
With
this
information
hand,
synthesized
26
PROTACs
based
on
alkyl
linkers
different
lengths
rigidity.
formation
ternary
was
validated
FRET-based
biochemical
assay
vitro
ubiquitination
assay.
14,
20,
22,
24,
30,
featuring
lengths,
50%
higher
degradation
METTL3
and/or
METTL14
measured
Western
blot
MOLM-13
cells.
They
also
substantial
three
AML
lines
prostate
cancer
line
PC3.
Journal of Cellular Physiology,
Год журнала:
2024,
Номер
239(5)
Опубликована: Март 19, 2024
Abstract
Proteolysis
Targeting
Chimeras
(PROTACs)
represent
a
significant
advancement
in
therapeutic
drug
development
by
leveraging
the
ubiquitin‐proteasome
system
to
enable
targeted
protein
degradation,
particularly
impacting
oncology.
This
review
delves
into
various
types
of
PROTACs,
such
as
peptide‐based,
nucleic
acid‐based,
and
small
molecule
each
addressing
distinct
challenges
degradation.
It
also
discusses
innovative
strategies
like
bridged
PROTACs
conditional
switch‐activated
offering
precise
targeting
previously
“undruggable”
proteins.
The
potential
extends
beyond
oncology,
with
ongoing
research
technological
advancements
needed
maximize
their
potential.
Future
progress
this
field
relies
on
interdisciplinary
collaboration
integration
advanced
computational
tools
open
new
treatment
avenues
across
diseases.
Advanced NanoBiomed Research,
Год журнала:
2024,
Номер
4(4)
Опубликована: Фев. 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.
Cancer
stem
cells
(CSCs)
with
hyperactivated
signal
transducer
and
activator
of
transcription
3
(STAT3)
are
a
major
driver
hepatocellular
carcinoma
(HCC).
Herein,
we
report
nanointegrative
proteolysis-targeting
chimera
(PROTAC)-based
STAT3
degradation
strategy
that
enables
efficient
chemical
reprogramming
HCC-associated
CSCs,
which
potently
inhibits
CSC
growth
while
evoking
anti-HCC
immune
responses.
The
PROTAC
prodrug
was
synthesized
by
conjugating
the
binding
domain
(inS3)
thioketal-caged
E3
ligase
ligand
(VL-TK)
via
an
oligo(ethylene
glycol)
linker
(OEG)
tuned
length
flexibility
encapsulating
it
in
cRGD-modified
cationic
liposomes
for
CSC-targeted
delivery
facilitating
their
lysosomal
escape.
prodrugs
were
activated
upregulated
ROS
levels
CSCs
efficiently
degraded
reprogramming,
would
not
only
impair
stemness
features
but
also
remodel
immunosuppressive
TME
into
immunosupportive
state
to
boost
immunity.
This
provides
approach
improving
HCC
treatment
clinics.
Nano Letters,
Год журнала:
2024,
Номер
24(3), С. 950 - 957
Опубликована: Янв. 10, 2024
Sonodynamic
therapy
(SDT)
was
hampered
by
the
sonosensitizers
with
low
bioavailability,
tumor
accumulation,
and
therapeutic
efficiency.
In
situ
responsive
sonosensitizer
self-assembly
strategy
may
provide
a
promising
route
for
cancer
sonotheranositics.
Herein,
an
intelligent
sonotheranostic
peptide–purpurin
conjugate
(P18-P)
is
developed
that
can
self-assemble
into
supramolecular
structures
via
self-aggregation
triggered
rich
enzyme
cathepsin
B
(CTSB).
After
intravenous
injection,
versatile
probe
could
achieve
deep
tissue
penetration
because
of
sequence
P18-P.
More
importantly,
CTSB-triggered
strongly
prolonged
retention
time,
amplified
photoacoustic
imaging
signal
sensitive
CTSB
detection,
boosted
reactive
oxygen
species
advanced
SDT,
evoking
specific
sonotheranostics.
This
serve
as
efficient
platform
early
diagnosis
activity
effective
therapy.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Ноя. 18, 2024
Abstract
The
rise
of
rational
strategies
in
nanomedicine
development,
such
as
high-throughput
methods
and
computer-aided
techniques,
has
led
to
a
shift
the
design
discovery
patterns
nanomedicines
from
trial-and-error
mode
mode.
This
transition
facilitates
enhancement
efficiency
preclinical
pipeline
nanomaterials,
particularly
improving
hit
rate
nanomaterials
optimization
promising
candidates.
Herein,
we
describe
directed
evolution
driven
by
data
accelerate
with
high
delivery
efficiency.
Computer-aided
are
introduced
detail
one
cutting-edge
directions
for
development
nanomedicines.
Ultimately,
look
forward
expanding
tools
using
multidisciplinary
approaches.
Rational
may
potentially
boost
next-generation
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(34)
Опубликована: Июнь 5, 2024
Although
self-assembly
has
emerged
as
an
effective
tool
for
fabricating
biomaterials,
achieving
precise
control
over
the
morphologies
and
functionalities
of
resultant
assemblies
remains
ongoing
challenge.
Inspired
by
copper
peptide
naturally
present
in
human
plasma,
this
study,
we
designed
a
synthetic
precursor,
FcGH.
FcGH
can
self-assemble
via
two
distinct
pathways:
spontaneous
Cu
International Journal of Biological Macromolecules,
Год журнала:
2024,
Номер
275, С. 133680 - 133680
Опубликована: Июль 4, 2024
Proteolysis
targeting
chimeras
(PROTACs)
can
use
the
intrinsic
protein
degradation
system
in
cells
to
degrade
pathogenic
target
proteins,
and
are
currently
a
revolutionary
frontier
of
development
strategy
for
tumor
treatment
with
small
molecules.
However,
poor
water
solubility,
low
cellular
permeability,
off-target
side
effects
most
PROTACs
have
prevented
them
from
passing
preclinical
research
stage
drug
development.
This
requires
appropriate
delivery
systems
overcome
these
challenging
hurdles
ensure
precise
towards
site.
Therefore,
combination
multifunctional
will
open
up
new
directions
targeted
proteins.
In
this
review,
we
systematically
reviewed
design
principles
recent
advances
various
systems.
Moreover,
constructive
strategies
developing
were
proposed
comprehensively.
review
aims
deepen
understanding
drugs
promote
further
system.
Chemical Society Reviews,
Год журнала:
2024,
Номер
53(19), С. 9582 - 9608
Опубликована: Янв. 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