ACS Biomaterials Science & Engineering,
Год журнала:
2024,
Номер
11(1), С. 429 - 441
Опубликована: Дек. 19, 2024
Chemotherapeutic
drugs
often
fail
to
localize
efficiently
tumors
when
administered
intravenously,
causing
off-target
effects.
This
study
proposes
an
autologous
erythrocyte
(ER)-anchoring
strategy
improve
chemotherapy
efficacy
and
reduce
side
Utilizing
a
modified
hemodialysis
instrument,
closed-system
drug-transfer
device
was
developed
for
ER
procurement
immunogenicity
mitigation.
Doxorubicin
(DOX)
indocyanine
green
(ICG)
were
encapsulated
in
ERs
then
with
DSPE-PEG-FA.
The
final
product,
DOX-ICG@ER-D,
reintroduced
into
circulation
enhance
chemotherapy.
These
obtained
DOX-ICG@ER-D
showed
good
stability,
minimal
cardiotoxicity,
extended
time.
Compared
free
DOX,
had
higher
accumulation
of
DOX
hepatocellular
carcinoma
the
release
could
be
controlled
by
laser
irradiation.
Tumor-bearing
rats
treated
these
demonstrated
improved
antitumor
reduced
cardiotoxicity.
Thus,
this
ER-anchoring
offers
promising
alternative
intravenous
clinic.
Biomacromolecules,
Год журнала:
2024,
Номер
25(8), С. 4991 - 5007
Опубликована: Авг. 1, 2024
The
GPS-Nanoconveyor
(MA-NV@DOX-Cas13a)
is
a
targeted
nanoplatform
designed
for
the
imaging
and
gene/chemotherapy
synergistic
treatment
of
melanoma.
It
utilizes
rolling
circle
amplification
(RCA)
products
as
scaffold
to
construct
DNA
"Nanoconveyor"
(NV),
which
incorporates
multivalent
aptamer
(MA)
"GPS",
encapsulates
doxorubicin
(DOX)
in
transporter,
equips
it
with
CRISPR/Cas13a
ribonucleoproteins
(Cas13a
RNP).
Carrying
MA
enhances
ability
recognize
overexpressed
receptor
nucleolin
on
B16
cells,
enabling
precise
delivery
MA-NV@DOX-Cas13a
through
receptor-mediated
endocytosis.
activation
signal
transducer
activator
transcription
3
(STAT3)
cancer
cells
triggers
cis-cleavage
CRISPR/Cas13a,
initiating
its
trans-cleavage
function.
Additionally,
deoxyribonuclease
I
(DNase
I)
degrades
MA-NV,
releasing
DOX
intracellular
chemotherapeutic
agent.
Experiments
demonstrate
superior
capabilities
this
versatile
cellular
co-treatment
while
highlighting
advantages
these
nanodrug
systems
mitigating
side
effects.
Doxorubicin
(DOX)
is
an
anthracycline
with
potent
antitumor
properties
and
rare
yet
serious
cardiotoxic
side
effects
that
limit
its
clinical
application.
The
sigma-1
receptor
a
stress-triggered
chaperone
often
dysregulated
in
diseases
has
known
cardioprotective
effects.
Although
anti-oxidative
stress
anti-apoptotic
have
been
demonstrated,
effectiveness
DOX-induced
cardiotoxicity
never
explored.
This
study
investigated
the
potential
role
of
activated
murine
model
to
elucidate
receptor's
mechanism
action.
We
established
C57BL/6
mice
by
daily
intraperitoneal
injections
fluvoxamine
(Flv)
for
4
consecutive
weeks
activate
weekly
DOX
at
5
mg/kg
3
weeks.
performed
vitro
experiments
using
cardiomyocytes
neonatal
Sprague–Dawley
rats
verify
protective
effect
receptor.
found
expression
heart
decreased
DOX-treated
mice,
activating
Flv
improved
cardiac
function.
Moreover,
pretreatment
inhibited
cardiomyocyte
apoptosis
endoplasmic
reticulum
increased
Bcl2
regulator
(Bcl2),
effectively
alleviating
pathophysiological
manifestations
mice.
In
addition,
exerted
modulating
through
PRKR-like
kinase
(PERK)
signaling
pathway.
It
also
reduced
mitochondrial
contact
alleviated
calcium
overload
IP3R-VDAC1-MCU
conclusion,
our
emphasizes
therapeutic
receptors
against
cardiotoxicity,
suggesting
as
targets
this
disease.
Frontiers in Oncology,
Год журнала:
2024,
Номер
14
Опубликована: Апрель 19, 2024
Detrimental
side
effects
of
drugs
like
doxorubicin,
which
can
cause
cardiotoxicity,
pose
barriers
for
preventing
cancer
progression,
or
treating
early
through
molecular
interception.
Extracellular
vesicles
(EVs)
are
valued
their
potential
as
biomarkers
human
health,
chemical
and
carcinogenesis,
therapeutics
to
treat
disease
at
the
cellular
level.
EVs
released
both
during
normal
growth
in
response
toxicity
death,
playing
key
roles
communication.
Consequently,
may
hold
promise
precision
prevent
offset
damaging
off-target
chemotherapeutics.
have
impending
cardiotoxicity
induced
by
chemotherapies
cardioprotective
therapeutic
agents.
However,
also
mediate
cardiotoxic
cues,
depending
on
identity
past
events
parent
cells.
Understanding
how
signaling
is
critical
toward
implementing
agents
mitigate
chemotherapies.
For
example,
it
remains
unclear
mixtures
EV
populations
from
cells
exposed
toxins
undergoing
different
stages
cell
death
contribute
across
cardiac
tissues.
Here,
we
present
our
perspective
outlook
future
clinical
tools
chemotherapy-induced
Also,
discuss
heterogeneous
transient
exposures
toxicants
add
complexity
predicting
outcomes
exogenously
applied
EVs.
Elucidating
cargo
properties
change
dynamic
aid
prevention
anticancer
treatments
development
safer
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 22, 2024
Abstract
Doxorubicin
(DOX),
a
widely
used
chemotherapy,
extends
its
impact
beyond
cancer
cells,
notably
affecting
the
heart,
leading
to
substantial
concerns
about
DOX-induced
cardiotoxicity
(DIC).
However,
subclinical
DIC
remains
unresolved,
necessitating
advanced
cardio-protection
strategies
in
therapy.
Recent
research
explores
carvacrol
(CAR),
natural
substance
with
antioxidant
and
anti-inflammatory
properties,
as
potential
shield
against
DIC.
further
exploration
is
warranted,
particularly
concerning
hypertrophy
cardiac
fibrosis.
This
study
investigated
CAR’s
cardioprotective
properties
H9c2
cardiomyocytes
rats.
Induction
DOX
reduced
cardiomyocyte
viability,
while
pretreatment
0.01
µg/mL
CAR
enhanced
viability
of
cardiomyocytes.
Meanwhile,
administration
induced
adverse
effects
rats,
causing
decreased
total
heart
weight
left
ventricular
mass,
lowered
blood
pressure.
also
caused
dysfunction,
lipid
peroxidation,
hypertrophy,
In
rat
models,
effectively
mitigated
reductions
pressure,
kept
function,
oxidative
stress,
enzymes
unaltered.
conclusion,
results
show
that
could
be
an
adjuvant
reduce
by
ameliorating
fibrosis
hypertrophy.
