A Targeted and Responsive Nanoprodrug Delivery System for Synergistic Glioma Chemotherapy
Small,
Год журнала:
2024,
Номер
20(30)
Опубликована: Март 3, 2024
Abstract
Doxorubicin
(DOX)
is
widely
used
as
a
chemotherapeutic
agent
for
both
hematologic
and
solid
tumors
reasonable
candidate
glioma
treatment.
However,
its
effectiveness
hindered
by
significant
toxicity
drug
resistance.
Moreover,
the
presence
of
blood–brain
barrier
(BBB)
brings
crucial
challenge
to
therapy.
In
response,
GSH‐responsive
actively
targeted
nanoprodrug
delivery
system
(cRGD/PSDOX‐Cur@NPs)
are
developed.
this
system,
disulfide
bond‐bridged
DOX
prodrug
(PEG‐SS‐DOX)
designed
release
specifically
in
high
glutathione
(GSH)
tumor
environment,
markedly
reducing
cardiotoxicity
associated
with
DOX.
To
further
address
resistance,
curcumin,
serving
P‐glycoprotein
(P‐gp)
inhibitor,
effectively
increased
cellular
concentration.
Consequently,
cRGD/PSDOX‐Cur@NPs
exhibited
synergistic
anti‐tumor
effects
vitro.
Furthermore,
vivo
experiments
validated
superior
BBB
penetration
brain‐targeting
abilities
cRGD/PSDOX‐Cur@NPs,
showcasing
remarkable
potential
treating
subcutaneous
orthotopic
gliomas.
This
research
underscores
that
presents
novel
approach
inhibiting
while
addressing
resistance
systemic
toxicity.
Язык: Английский
How to optimize the immune checkpoint blockade therapy for cancers?
ONCOLOGIE,
Год журнала:
2024,
Номер
26(3), С. 343 - 348
Опубликована: Март 16, 2024
Abstract
The
realm
of
cancer
therapy
has
been
profoundly
altered
with
the
emergence
immune
checkpoint
blockade
(ICB)
therapy,
providing
improved
survival
prospects
for
many
patients
some
cancers.
However,
challenge
achieving
efficient
or
sustained
therapeutic
benefits
underscores
critical
imperative
to
optimize
ICB
strategies.
This
review
elucidates
pivotal
role
predictive
biomarkers
in
optimizing
precision
deciphering
intricate
dynamics
associated
response
heterogeneity.
Furthermore,
it
critically
examines
application
nanotechnology-driven
drug
delivery
as
a
promising
avenue
amplify
efficacy,
facilitating
controlled
and
targeted
release.
Recognizing
comprehensive
dynamic
interplay
among
tumor
cells,
stromal
cells
catalyzed
transformative
advances
reverse
translational
research.
approach
enables
researchers
gain
insights
into
underlying
mechanisms
responses,
resistance
mechanisms.
convergence
biomarkers,
revolutionary
nanotechnology,
research
emerges
an
indispensable
focal
point,
propelling
frontiers
oncology
within
complex
landscape
therapy.
Язык: Английский
Iterative Design of a Prodrug Nanocarrier for Cell Cycle Arrest, Immune Modulation, and Enhanced T Cell Infiltration for Colon Cancer Therapy
Nano Letters,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 10, 2025
Recent
advancements
in
cancer
therapy
have
highlighted
the
dual
role
of
cyclin-dependent
kinase
4/6
inhibitors
(CDK4/6i)
both
cell
cycle
regulation
and
immune
activation.
However,
applying
CDK4/6i
to
immunologically
unfavorable
tumors
is
challenging
due
complex
tumor
microenvironment
(TME),
characterized
by
inadequate
T
recruitment
exclusion
mechanisms
that
hinder
an
effective
antitumor
immunity.
In
this
work,
we
iteratively
designed
prodrug
liposomal
nanocarriers
integrate
multiple
functions:
inhibition
through
encapsulation
CDK4/6i,
activation
via
concurrent
delivery
oral
gavage-inducing
chemotherapy
agent,
overcoming
incorporation
a
cholesterol
prodrug.
This
iterative
nanocarrier
design
effectively
improves
pharmacokinetic
profile
overcomes
immunosuppressive
TME,
achieves
superior
efficacy,
synergizes
with
checkpoint
provide
lasting
effects
various
colon
animal
models.
Язык: Английский
Piezo‐Electrons Induced Endoplasmic Reticulum Protein Misfolding to Enhance Immune Checkpoint Blockage Cancer Therapy
Advanced Functional Materials,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 14, 2025
Abstract
The
endoplasmic
reticulum
(ER)
is
a
crucial
organelle
in
eukaryotic
cells
that
regulates
protein
synthesis,
folding,
and
transport,
playing
vital
role
maintaining
homeostasis
functions.
Tumor
evade
the
immune
surveillance
killing
of
body
by
synthesizing
checkpoint
proteins
ER,
thereby
inhibiting
T
cell‐mediated
antitumor
responses
enhancing
tumor
tolerance,
leading
to
poor
efficacy
cancer
immunotherapy.
Herein,
an
ultrasound‐triggered
piezo‐nanomedicine
designed
with
targeting
function
(BTO
v
‐T
ER
)
achieve
novel
blockade
therapy.
Under
ultrasound
irradiation,
BTO
releases
piezo‐electrons
reducing
properties
disrupt
redox
cell
reticulum,
inducing
misfolding
apoptosis,
which
activates
response.
Meanwhile,
due
abnormal
folding
expression
proteins,
such
as
Programmed
death
ligand
1
(PD‐L1)
downregulated,
reactivating
promoting
strategy
interfering
processing
various
within
via
piezo‐catalysis
provides
approach
for
Язык: Английский
Saponin Gallate-Loaded Gd-Doped Zinc–Gallium Layered Double Hydroxides (Zn/Ga@Gd-LDH) Nanocarrier for Attenuating NF-κB-Mediated Inflammation
ACS Applied Materials & Interfaces,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 24, 2025
This
work
describes
a
drug
delivery
system
(DDS)
based
on
the
therapeutic
anti-inflammatory
efficacy
of
saponin
gallate
(SG),
combination
gallic
acid
and
saponin,
chemically
conjugated
via
an
ester
linkage.
formulation
was
loaded
onto
biocompatible
gadolinium-doped
zinc-gallium-layered
double
hydroxide
(Zn/Ga@Gd-LDH)
nanocarrier.
FT-IR,
XRD,
SEM,
HPLC
were
used
to
characterize
synthesized
materials.
UV-visible
spectroscopy
employed
investigate
release
from
SG-Zn/Ga@Gd-LDH
at
optimized
temperature
(45
°C)
pH
(5).
The
kinetic
behavior
nanoparticles
suggested
that
first-order
model
most
appropriate
for
profile.
regression
value
(R2)
0.96614
indicated
optimal
controlled
effectiveness
minimal
adverse
effects
over
54
h.
in
vitro
vivo
models
confirmed
drug-loaded
nanocarriers
exhibited
antioxidant,
anti-inflammatory,
anticancer
properties.
Western
blotting
analysis
abrogates
properties
by
halting
phosphorylation
pro-inflammatory
proteins
p-p65
decreasing
CRP
levels
involved
NF-κB
pathway.
effect
reducing
secretion
proinflammatory
cytokines.
treatment
against
acute
CCl4-induced
liver
injury
showed
potential
histological
parameters'
study.
Radiolabeling
with
99mTc
carried
out
determine
its
biodistribution.
chromatographic
results
promising
radiolabeling
up
90%
percentages.
SPECT-CT
imaging
ex
gamma
counting
Wistar
rats
revealed
different
clearance
rates
nanoparticles,
aiding
evaluation
nanosystem.
designed
also
demonstrated
antioxidant
due
SG
compound
having
IC50
127.45
μg/mL
free
radical
scavenging
activity.
Ga@Gd-LDH
tumor-suppressing
ability
79.89
±
3.91%
viable
cells
breast
cancer
MCF-7
cells.
developed
could
thus
be
conducive
strategy
inflammatory
diseases.
Язык: Английский
Comparison of Protocols to Test Peptide Stability in Blood Plasma and Cell Culture Supernatants
ACS Pharmacology & Translational Science,
Год журнала:
2024,
Номер
7(11), С. 3618 - 3625
Опубликована: Окт. 14, 2024
Due
to
their
high
specificity,
peptides
are
promising
candidates
in
drug
development,
but
fast
degradation
often
limits
biological
activity.
Thus,
a
short
half-life
is
one
of
the
major
challenges
development
new
peptide
therapeutics.
Moreover,
enzymatic
cleavage
can
be
reason
for
misleading
results
assays.
Peptide
stability
assays
typically
consist
incubation,
precipitation,
and
detection
steps.
However,
current
methods
differ
greatly
regarding
these
three
steps,
thus
limiting
compatibility.
Here,
we
systematically
evaluate
different
parameters
First,
quantified
compared
analyte
loss
during
precipitation
plasma
proteins.
Especially,
broadly
used
by
strong
acids
was
found
unsuitable,
while
mixtures
organic
solvents
preserved
more
further
analysis.
Next,
four
fluorescently
labeled
model
analyzed
blood
two
cell
culture
supernatants.
Strong
variation
dynamics
patterns
found.
Finally,
evaluated
role
fluorescent
labeling
on
with
isotopic
labels,
underlining
individual
advantages
both
methods.
Altogether,
data
provide
important
analyzing
comparing
stability.
Язык: Английский
Nanomotors activating both cGAS-STING pathway and immune checkpoint blockade for tumor therapy and bioimaging
Talanta,
Год журнала:
2024,
Номер
284, С. 127258 - 127258
Опубликована: Ноя. 20, 2024
Язык: Английский
Engineering Peptide-Based Molecular Baits for Targeted Fishing and Protein Profiling of Exosomes as a Liquid Biopsy for Gastrointestinal Adenocarcinoma
Analytical Chemistry,
Год журнала:
2024,
Номер
97(1), С. 741 - 748
Опубликована: Дек. 30, 2024
High-performance
isolation
of
exosomes
as
a
promising
liquid
biopsy
target
is
great
importance
for
both
fundamental
research
and
clinical
applications.
This
is,
however,
challenged
by
the
prevalent
heterogeneity
highly
complex
nature
biosamples.
Here,
we
introduce
use
CD81-targeting
peptide
building
block
tailoring
molecular
baits
exosome
payload
analysis
in
biofluids.
To
explore
full
potential
multivalent
interactions,
peptide-functionalized
affinity
interfaces
were
covalently
engineered
with
varied
assembling
topology,
flexibility,
local
density
recognition
motif.
Capable
best
fitting
surface
conformation
CD81
on
curved
membranes,
dual-layered
capture
interface
(Exo-PepTrap2)
tandem
bivalent
decoration
outperforms
monolayered
branched
architectures.
Enabled
multivalency-enhanced
reaction
antifouling
ability,
Exo-PepTrap2
achieved
high
yield
purity
targeted
fishing
cell
culture
media
urine
samples.
By
integration
mass
spectrometry-based
proteomic
profiling,
differentially
expressed
proteins
efficiently
identified
harvested
biomarkers
gastrointestinal
adenocarcinoma.
CD81-targeted
platform
provides
new
viewpoint
multivalency-based
versatile
tool
to
information
precise
medicine.
Язык: Английский