Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 12, 2024
Abstract
Cuproptosis
is
an
emerging
regulated
cell
death
that
depends
on
the
intracellular
copper
ion
and
mitochondrial
respiration,
showing
great
potential
in
cancer
treatment.
However,
increasing
specific
accumulation
of
ions
mitochondria
while
simultaneously
enhancing
respiration
are
highly
needed
still
a
major
challenge
to
promote
cuproptosis.
Herein,
lactate
dehydrogenase
(LDH)
inhibitor
galloflavin
(GF)
self-assembles
with
ionophore
elesclomol
(ES)
through
ion-driven
cooperative
coordination
form
GF/CuES
nanoparticles,
synergistically
targeting
anaerobic
glycolysis
boost
cuproptosis-immunotherapy.
After
cellular
internalization,
nanoparticles
responsively
dissociate
release
Cu2+
ES,
co-transporting
into
collaboratively
trigger
cuproptosis,
which
subsequently
evokes
immunogenic
(ICD).
Notably,
liberated
GF
leads
effective
LDH
suppression,
not
only
further
amplifies
cuproptosis
via
disrupting
but
also
reduces
production,
thus
alleviating
immunosuppressive
tumor
microenvironment
augmenting
anti-tumor
immunity
driven
by
ICD.
Thus,
exhibit
strong
antitumor
effects
cooperatively
glycolysis,
immunotherapy,
offering
unique
opportunity
enhance
treatment
strategies.
International Journal of Nanomedicine,
Год журнала:
2025,
Номер
Volume 20, С. 1147 - 1169
Опубликована: Янв. 1, 2025
Phototherapy
has
remarkable
advantages
in
cancer
treatment,
owing
to
its
high
efficiency
and
minimal
invasiveness.
Indocyanine
green
(ICG)
plays
an
important
role
photo-mediated
therapy.
However,
it
several
disadvantages
such
as
poor
stability
aqueous
solutions,
easy
aggregation
of
molecules,
short
plasma
half-life.
This
study
aimed
develop
efficient
nanoplatform
enhance
the
effects
We
developed
a
novel
bio-nanoplatform
by
integrating
edible
ginger-derived
exosome-like
nanoparticles
(GDNPs)
photosensitizer,
ICG
(GDNPs@ICG).
GDNPs
were
isolated
from
ginger
juice
loaded
with
co-incubation.
The
size
distribution,
zeta
potential,
morphology,
total
lipid
content,
drug
release
behavior
GDNPs@ICG
characterized.
photothermal
performance,
cellular
uptake
cytotoxicity,
anti-tumor
effects,
mechanism
action
investigated
both
vitro
vivo.
taken
up
tumor
cells
via
lipid-dependent
pathway.
When
irradiated
808
nm
NIR
laser,
generated
levels
ROS,
MDA,
local
hyperthermia
within
tumor,
which
caused
peroxidation
ER
stress,
thus
enhancing
breast
therapy
effect.
Furthermore,
vivo
studies
demonstrated
that
engineered
significantly
inhibited
growth
presented
limited
toxicity.
Moreover,
detecting
expression
CD31,
N-cadherin,
IL-6,
IFN-γ,
CD8,
p16,
p21,
p53
tissues,
we
found
substantially
reduced
angiogenesis,
metastasis,
activated
immune
response,
promoted
cell
senescence
tumor.
Our
enhanced
therapeutic
effect
could
be
alternative
for
precise
phototherapy.
Hepatocellular
carcinoma
(HCC),
the
most
common
type
of
liver
tumor,
is
a
leading
cause
cancer-related
deaths,
and
incidence
cancer
still
increasing
worldwide.
Curative
hepatectomy
or
transplantation
only
indicated
for
small
population
patients
with
early-stage
HCC.
However,
HCC
are
not
candidates
radical
resection
due
to
disease
progression,
choice
conventional
tyrosine
kinase
inhibitor
drug
sorafenib
as
first-line
treatment.
In
past
few
years,
immunotherapy,
mainly
immune
checkpoint
inhibitors
(ICIs),
has
revolutionized
clinical
strategy
Combination
therapy
ICIs
proven
more
effective
than
sorafenib,
trials
have
been
conducted
apply
these
therapies
patients.
Despite
significant
progress
in
molecular
mechanisms
behind
it
remain
unclear,
resistance
often
challenging
overcome.
Several
studies
pointed
out
that
complex
intercellular
communication
network
microenvironment
regulates
tumor
escape
response.
This
underscores
urgent
need
analyze
review
describes
immunosuppressive
cell
populations
HCC,
well
related
trials,
aiming
provide
insights
next
generation
precision
immunotherapy.
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(4), С. 1440 - 1440
Опубликована: Фев. 8, 2025
Antibody-based
immune-stimulating
drugs
(ABIs)
represent
a
transformative
frontier
in
cancer
immunotherapy,
designed
to
reshape
the
tumor
microenvironment
and
overcome
immune
suppression.
This
study
highlighted
recent
advances
ABIs,
including
antibody
conjugates
(ISACs),
bispecific
antibodies
(BsAbs),
checkpoint
blockade
enhancers,
with
focus
on
their
mechanisms
of
action,
clinical
advancements,
challenges.
Preclinical
findings
revealed
that
ISACs
effectively
boost
overall
anti-cancer
immunity
by
reprogramming
tumor-associated
macrophages,
enhancing
T
cell
activation,
engaging
other
pathways.
Similarly,
BsAbs
redirect
cells
tumors,
achieving
significant
regression.
Additionally,
artificial
intelligence
(AI)
is
revolutionizing
development
ABIs
optimizing
drug
design,
identifying
novel
targets,
accelerating
preclinical
validation,
enabling
personalized
therapeutic
strategies.
Despite
these
challenges
remain,
resistance
off-target
effects.
Future
research
should
prioritize
next-generation
multifunctional
antibodies,
AI-driven
innovations,
combination
therapies
enhance
efficacy
expand
applications.
Connecting
gaps
could
unlock
full
potential
upgrading
treatment
improving
outcomes
for
patients
refractory
or
resistant
tumors.
International Immunopharmacology,
Год журнала:
2025,
Номер
150, С. 114265 - 114265
Опубликована: Фев. 16, 2025
Macrophage-mediated
inflammation
is
closely
linked
to
the
pathogenesis
of
acute
kidney
injury
(AKI)
and
shift
macrophages
a
pro-inflammatory
phenotype
being
reliant
on
glycolytic
metabolism.
Galloflavin,
polyphenol
derived
from
tea,
functions
as
lactate
dehydrogenase
A
(LDHA)
inhibitor,
effectively
obstructing
metabolic
pathways.
However,
specific
immunometabolic
regulatory
galloflavin
in
remain
unclear.
Here,
we
observed
that
drives
alleviation
metabolism
levels
lipopolysaccharide
(LPS)-induced
(RAW264.7
cells
human
peripheral
blood
mononuclear
cells-derived
macrophages)
through
downregulation
LDHA
expression,
thereby
inhibiting
macrophage
conversion
reducing
release
inflammatory
cytokines.
overexpression
counteracts
effects
macrophages.
In
addition,
vivo
experiments
protective
effect
against
cecal
ligation
puncture
(CLP)
cisplatin-induced
renal
injury.
The
ability
inhibit
glycolysis
macrophages,
regulating
their
phenotypic
transition
during
AKI
was
further
validated
isolation
primary
This
intervention
ultimately
ameliorated
response
decelerated
progression
AKI.
Collectively,
confers
protection
by
suppressing
LDHA-dependent
mechanism,
positioning
it
potential
therapeutic
option
for
future.
Biomolecules,
Год журнала:
2024,
Номер
14(10), С. 1202 - 1202
Опубликована: Сен. 24, 2024
Lactate
accumulation
and
macrophage
infiltration
are
pivotal
features
of
both
chronic
inflammation
cancer.
Lactate,
once
regarded
merely
as
an
aftereffect
glucose
metabolism,
is
now
gaining
recognition
for
its
burgeoning
spectrum
biological
roles
immunomodulatory
significance.
Recent
studies
have
evidenced
that
macrophages
display
divergent
immunophenotypes
in
different
diseases,
which
play
a
role
disease
management
by
modulating
polarization
within
the
microenvironment.
The
specific
patterns
high-lactate
environment
their
contribution
to
progression
cancer
remain
contentious.
This
review
presents
current
evidence
on
crosstalk
lactate
Additionally,
we
provide
in-depth
exploration
yet
enigmatic
mechanisms
through
orchestrates
pathogenesis,
thereby
offering
novel
perspectives
development
targeted
therapeutic
interventions
Frontiers in Cardiovascular Medicine,
Год журнала:
2024,
Номер
11
Опубликована: Ноя. 27, 2024
Cardiovascular
disease
(CVD)
is
responsible
for
approximately
30%
of
annual
global
mortality
rates,
yet
existing
treatments
this
condition
are
considered
less
than
ideal.
Despite
being
previously
overlooked,
lactate,
a
byproduct
glycolysis,
now
acknowledged
its
crucial
role
in
the
cellular
functions
cardiovascular
system.
Recent
studies
have
shown
that
lactate
influences
proliferation,
differentiation,
and
activation
immune
cells
through
modulation
post-translational
protein
modifications,
thereby
affecting
development
prognosis
disease.
Consequently,
there
has
been
notable
increase
interest
towards
drug
targets
targeting
lactylation
cells,
prompting
further
exploration.
In
light
swift
advancements
domain,
review
article
dedicated
to
examining
potential
regulating
lactylation,
with
aim
enhancing
comprehension
intricate
field.
Advanced Healthcare Materials,
Год журнала:
2024,
Номер
14(4)
Опубликована: Дек. 17, 2024
Interference
with
glycolysis
metabolism
not
only
promotes
the
efficient
sensitization
of
cuproptosis,
but
also
amplifies
cytotoxic
T
cell
functions
and
proliferations,
thus
contributing
to
relieve
immunosuppressive
tumor
microenvironment.
However,
synergistic
mechanism
design
multicomponent
nanoformulations
involving
these
three
pathways
have
yet
been
explored.
a
copper-coordinated
nanoassembly
(designated
as
Cu-GM)
is
reported
here
that
integrates
lactate
dehydrogenase
inhibitor,
galloflavin
(GF),
an
immune
checkpoint
myricetin
(MY),
boost
cancer
cuproptosis-immunotherapy.
These
results
suggest
Cu-GM
can
be
activated
by
endogenous
overexpressed
glutathione
release
Cu+,
leading
abnormal
aggregation
lipoylated
proteins
iron-sulfur
cluster
loss,
which
triggers
proteotoxic
stress
cuproptosis.
Meanwhile,
released
GF
inhibits
amplify
cuproptosis
efficacy
achieves
effective
depletion,
alleviating
effects
lactate.
Notably,
killed
cells
induce
immunogenic
death
evoke
anti-tumor
immunity,
further
augmented
MY-mediated
blockade.
Taken
together,
first
anticancer
synergy
metabolism,
immunotherapy
presented,
showcasing
remarkable
in
vivo
antitumor
encouraging
exploration
rational
multimodal
treatment
approach.
