International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(3), С. 1238 - 1238
Опубликована: Янв. 31, 2025
Immune
checkpoint
blockade
therapy,
represented
by
anti-PD-1/PD-L1
monoclonal
antibodies,
has
significantly
changed
the
immunotherapy
landscape.
However,
treatment
is
still
limited
unsatisfactory
response
rates,
immune-related
adverse
effects,
and
drug
resistance.
Current
studies
have
established
that
glycosylation,
a
common
post-translational
modification,
crucial
in
promoting
cancer
progression
immune
invasion.
Targeting
aberrant
glycosylation
cancers
presents
precision
medicine
regimens
for
monitoring
developing
personalized
medicine.
Notably,
checkpoints
PD-1
PD-L1
are
highly
glycosylated,
which
affects
PD-1/PD-L1
interaction
binding
of
antibodies.
Recent
achievements
glycoscience
to
enhance
patient
outcomes,
referred
as
glycotherapy,
underscored
their
high
potency
advancing
therapies,
i.e.,
glycoengineered
antibodies
with
improved
toward
PD-1/PD-L1,
pharmaceutic
inhibitors
core
fucosylation
sialylation,
synergistic
antibody-sialidase
conjugate.
This
review
briefly
introduces
axis
highlights
fundamental
applied
advances
improve
immunoblockade
therapies.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(20), С. 13805 - 13816
Опубликована: Март 29, 2024
Cuproptosis,
a
copper-dependent
cell
death
process,
has
been
confirmed
to
further
activate
the
immune
response
and
mediate
resistance.
However,
hypoxic
tumor
microenvironment
hampers
cuproptosis
sensitivity
suppresses
body's
antitumor
response.
Herein,
we
have
successfully
immobilized
functionalized
catalase
(CAT)
with
long
single-stranded
DNA
containing
polyvalent
CpG
sequences
through
rolling
circle
amplification
(RCA)
techniques,
obtaining
an
enzyme-cored
spherical
nucleic
acid
nanoplatform
(CAT-ecSNA-Cu)
deliver
copper
ions
for
cuproptosis.
The
presence
of
long-stranded
DNA-protected
CAT
enhances
mitochondrial
respiration
by
catalyzing
conversion
H2O2
O2,
thereby
sensitizing
Meanwhile,
increased
oxygenation
expression
hypoxia-inducible
factor-1
(HIF-1)
protein,
resulting
in
alleviation
immunosuppressive
microenvironment.
Of
note,
induces
immunogenic
(ICD),
which
facilitates
dendritic
(DC)
maturation
antigen
presentation
polyCpG-supported
Toll-like
receptor
9
(TLR9)
activation.
Furthermore,
cuproptosis-induced
PD-L1
upregulation
cells
complements
checkpoint
blockers
(αPD-L1),
enhancing
immunity.
strategy
cuproptosis-mediated
responses
alleviating
hypoxia
effectively
promotes
activation
proliferation
effector
T
cells,
ultimately
leading
long-term
immunity
against
cancer.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(44), С. 30033 - 30045
Опубликована: Окт. 28, 2024
Cuproptosis,
a
recently
identified
form
of
copper-dependent
cell
death,
shows
promising
tumor
suppressive
effects
with
minimal
drug
resistance.
However,
its
therapeutic
efficacy
is
hampered
by
dependence
on
copper
ions
and
the
glutathione
(GSH)-rich
microenvironment
in
tumors.
Here,
we
have
developed
polyvalent
aptamer
nanodrug
conjugates
(termed
CuPEs@PApt)
nucleosome-like
structure
to
improve
cuproptosis
therapy
exploiting
mitochondrial
overload
GSH
depletion.
Polyvalent
(PApt),
comprising
epithelial
adhesion
molecule
aptamers
for
targeting
repetitive
PolyT
sequences
chelation,
facilitates
efficient
loading
targeted
delivery
peroxide-Elesclomol
nanodots
(CuPEs).
Upon
internalization
cells,
Elesclomol
released
from
CuPEs@PApt
accumulates
mitochondria
initiate
cuproptosis,
while
lysosomal
degradation
CuP
generates
exogenous
Cu2+
H2O2,
triggering
Fenton-like
reaction
depletion
enhance
cuproptosis.
In
vitro
vivo
experiments
confirm
this
strategy
inducing
immunogenic
latter
contributing
activation
antitumor
immune
response
synergistic
growth
inhibition.
Journal of Personalized Medicine,
Год журнала:
2024,
Номер
14(1), С. 68 - 68
Опубликована: Янв. 4, 2024
The
revolutionary
progress
in
cancer
immunotherapy,
particularly
the
advent
of
immune
checkpoint
inhibitors,
marks
a
significant
milestone
fight
against
malignancies.
However,
majority
clinically
employed
inhibitors
are
monoclonal
antibodies
(mAbs)
with
several
limitations,
such
as
poor
oral
bioavailability
and
immune-related
adverse
effects
(irAEs).
Another
major
limitation
is
restriction
efficacy
mAbs
to
subset
patients,
which
triggered
extensive
research
efforts
identify
alternative
approaches
targeting
checkpoints
aiming
overcome
restricted
mAbs.
This
comprehensive
review
aims
explore
cutting-edge
developments
checkpoints,
focusing
on
both
small
molecule-
peptide-based
approaches.
By
delving
into
drug
discovery
platforms,
we
provide
insights
diverse
strategies
optimize
molecules
peptides
checkpoints.
In
addition,
discuss
recent
advances
nanomaterials
carriers,
providing
basis
for
development
platforms
immunotherapy.
Ongoing
focused
peptide-inspired
agents
paves
way
developing
orally
bioavailable
next-generation
immunotherapies.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(26), С. 17728 - 17737
Опубликована: Июнь 20, 2024
Targeted
protein
degradation
technology
holds
great
potential
in
biomedicine,
particularly
treating
tumors
and
other
protein-related
diseases.
Research
on
intracellular
using
molecular
glues
PROTAC
is
leading,
while
research
the
of
membrane
proteins
extracellular
through
lysosomal
pathway
still
preclinical
stage.
The
scarcity
useful
targets
an
immense
limitation
to
technological
advancement,
making
it
essential
explore
novel,
potentially
effective
approaches
for
targeted
degradation.
Here,
we
employed
glucose
transporter
Glut1
as
innovative
lysosome-targeting
receptor
devised
Glut1-Facilitated
Lysosomal
Degradation
(GFLD)
strategy.
We
synthesized
ligands
via
reversible
addition-fragmentation
chain
transfer
(RAFT)
polymerization
acquired
antibody-glycooligomer
conjugates
bioorthogonal
reactions
molecules,
utilized
management
PD-L1
high-expressing
triple-negative
breast
cancer.
a
exhibits
advancement
broader
array
medications
future.
JACS Au,
Год журнала:
2025,
Номер
5(2), С. 550 - 570
Опубликована: Фев. 6, 2025
Cell
surface
engineering
is
a
rapidly
advancing
field,
pivotal
for
understanding
cellular
physiology
and
driving
innovations
in
biomedical
applications.
In
this
regard,
DNA
nanotechnology
offers
unprecedented
potential
precisely
manipulating
functionalizing
cell
surfaces
by
virtue
of
its
inherent
programmability
versatile
functionalities.
Herein,
Perspective
provides
comprehensive
overview
emerging
trends
engineering,
focusing
on
key
nanostructure-based
tools,
their
roles
regulating
physiological
processes,
We
first
discuss
the
strategies
integrating
molecules
onto
surfaces,
including
attachment
oligonucleotides
higher-order
nanostructure.
Second,
we
summarize
impact
DNA-based
various
such
as
membrane
protein
degradation,
signaling
transduction,
intercellular
communication,
construction
artificial
components.
Third,
highlight
applications
DNA-engineered
targeted
therapies
cancer
inflammation,
well
capture/protection
diagnostic
detection.
Finally,
address
challenges
future
directions
nanotechnology-based
engineering.
This
aims
to
provide
valuable
insights
rational
design
contributing
development
precise
personalized
medicine.
The
development
of
immune
checkpoint
inhibitors,
especially
PDL1
antibodies,
has
revolutionized
cancer
therapy,
but
the
posttherapy
recycling
proteins
poses
a
significant
challenge
by
inducing
resistance
and
reducing
treatment
efficacy.
To
address
this,
we
introduce
an
integrin-driven,
lysosome-targeted
nanochimera,
composed
poly(glutamic
acid),
RGD
peptides,
is
designed
to
engage
target
protein,
with
αvβ3
integrin
binding
multivalent
peptides
direct
complex
through
endocytosomal
pathway
lysosome,
ensuring
degradation
blocking
its
recycling.
Our
in
vitro
vivo
experiments
demonstrate
that
these
nanochimeras
potently
activate
T-cell
antitumor
immunity
downregulating
expression
within
tumor
cells
tissues,
significantly
enhancing
efficacy
antibodies.
A
key
discovery
our
study
pivotal
role
facilitating
protein
degradation,
providing
valuable
insights
for
more
efficacious
sophisticated
immunotherapies.
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
67(8), С. 6027 - 6043
Опубликована: Апрель 10, 2024
Targeting
the
programmed
cell
death
protein-1
(PD-1)/programmed
death-ligand
1
(PD-L1)
pathway
has
evolved
into
one
of
most
promising
strategies
for
tumor
immunotherapy.
Thus
far,
multiple
monoclonal
antibody
drugs
have
been
approved
treating
a
variety
tumors,
while
development
small-molecule
PD-1/PD-L1
inhibitors
lagged
far
behind,
with
only
few
entering
clinical
trials.
In
addition
to
and
inhibitors,
reducing
expression
levels
PD-L1
attracted
extensive
research
interest
as
another
strategy
target
pathway.
Herein,
we
analyze
structures
mechanisms
molecules
that
reduce
classify
them
degraders
downregulators
according
whether
they
directly
bind
PD-L1.
Moreover,
discuss
potential
prospects
developing
PD-L1-targeting
based
on
these
molecules.
It
is
hoped
this
perspective
will
provide
profound
insights
discovery
potent
antitumor
immunity
drugs.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 20, 2024
Lysosome
targeting
chimeras
(LYTACs)
have
emerged
as
a
powerful
modality
that
can
eliminate
traditionally
undruggable
extracellular
tumor-related
pathogenic
proteins,
but
their
low
bioavailability
and
nonspecific
distribution
significantly
restrict
efficacy
in
precision
tumor
therapy.
Developing
LYTAC
system
selectively
target
tissues
enable
modular
design
is
crucial
challenging.
We
here
report
programmable
nanoplatform
for
tumor-specific
degradation
of
multipathogenic
proteins
using
an
intelligent
DNA
(IMTAC)
nanodevice.
employ
circular
origami
to
integrate
predesigned
multitarget
protein
binding
sites
pH-responsive
promoters
specifically
recognize
cell-surface
lysosome-shuttling
receptors
tissues.
By
precisely
manipulating
the
stoichiometry
modularity
ligands
diverse
IMTAC
nanodevice
enables
accurate
localization
delivery
into
tissues,
where
acidic
microenvironment
triggers
switch
activation,
multivalent
binding,
efficient
various
prespecified
proteins.
The
tissue-specificity
multiple
IMTACs
improve
drug
utilization
rate
while
reducing
off-target
effects.
Importantly,
this
demonstrates
capability
collabo-rative
EGFR
PDL1
tissue
combined
immunity
therapy
hepatocellular
carcinoma
(HCC),
resulting
obvious
necrosis
inhibition
growth
vivo
even
at
concentrations.
This
study
presents
unique
strategy
building
general,
intelligent,
modular,
simple
encoded
designing
medicine
degraders
developing
proprietary
antitumor
drugs.
ACS Applied Materials & Interfaces,
Год журнала:
2024,
Номер
16(17), С. 21571 - 21581
Опубликована: Апрель 18, 2024
Ag2S
quantum
dots
(QDs)
show
superior
optical
properties
in
the
NIR-II
region
and
display
significant
clinical
potential
with
favorable
biocompatibility.
However,
inherent
defects
of
low
targeting
poor
solubility
necessitate
practical
modification
methods
to
achieve
theranostics
QDs.
Herein,
we
used
rolling
circle
amplification
(RCA)
techniques
obtain
long
single-stranded
DNA
containing
PD-L1
aptamer
C-rich
palindromic
sequence.
The
sequences
can
specifically
chelate
Ag2+
thus
serve
as
a
template
result
biomimetic
mineralization
formation
pApt-Ag2S
These
QDs
enable
specific
illuminate
hot
tumors
high
expression
effectively,
serving
excellent
molecular
targeted
probes.
In
addition,
due
absorption
QDs,
exhibit
remarkable
photothermal
properties.
And
besides,
polyvalent
aptamers
recognize
protein
effectively
block
inhibitory
signal
on
T
cells,
enabling
efficient
through
synergistic
effect
therapy
immune
checkpoint
blocking
therapy.
Summary,
enhance
biological
stability
antibleaching
ability
using
template,
thereby
establishing
theranostic
platform
that
targets
high-expressing
inflamed
demonstrates
performance
both
vitro
vivo.