International Journal of Nanomedicine,
Год журнала:
2023,
Номер
Volume 18, С. 6367 - 6377
Опубликована: Ноя. 1, 2023
Purpose:
Molecular
targeted
therapy
is
one
of
the
most
pivotal
strategies
in
treatment
non-small
cell
lung
cancer,
yet
its
curative
effect
severely
compromised
by
poor
aqueous
solubility,
low
bioavailability
and
inadequate
tumor
accumulation
agents.
To
enhance
efficacy
agents,
we
demonstrate
a
novel
self-assemble
amphiphilic
molecule
based
on
erlotinib
as
an
effective
nanodrug
for
anti-cancer
treatment.
Methods:
An
composed
hydrophobic
hydrophilic
biotin
block
was
synthesized
characterized
nuclear
magnetic
resonance
(NMR)
well
high-resolution
mass
spectrometry
(HRMS).
Then,
nanoassemblies
molecules
are
formulated
using
nanoprecipitation
method.
Subsequently,
size,
morphology,
uptake,
anticancer
activity
vivo
distribution
newly
constructed
were
systematically
assessed
some
methods,
including
transmission
electron
microscopy
(TEM),
dynamic
light-scattering
(DLS),
flow
cytometry,
imaging
system
etc.
Results:
We
developed
nanoformulation
erlotinib,
which
possesses
high
drug
loading
45%.
With
features
well-defined
structure
small
obtained
could
be
effectively
accumulated
sites
rapidly
internalized
cancer
cells.
Finally,
erlotinib-based
showed
considerably
better
compared
to
free
both
vitro
vivo.
Moreover,
displayed
great
tolerability.
Conclusion:
Combining
advantageous
nanotechnology
self-assemble,
this
nanomedicine
constitutes
promising
therapeutic
candidate
This
study
also
underlines
potential
use
improving
reducing
toxicity,
become
general
strategy
preparation
nanodrugs
active
Keywords:
molecule,
self-assembling,
self-delivery
system,
International Journal of Nanomedicine,
Год журнала:
2024,
Номер
Volume 19, С. 7547 - 7566
Опубликована: Июль 1, 2024
Abstract:
Cancer
poses
a
significant
threat
to
human
life
and
health.
Chemotherapy
is
currently
one
of
the
effective
cancer
treatments,
but
many
chemotherapy
drugs
have
cell
toxicity,
low
solubility,
poor
stability,
narrow
therapeutic
window,
unfavorable
pharmacokinetic
properties.
To
solve
above
problems,
target
drug
delivery
tumor
cells,
reduce
side
effects
drugs,
an
anti-tumor
system
based
on
microenvironment
has
become
focus
research
in
recent
years.
The
construction
reduction-sensitive
nanomedicine
disulfide
bonds
attracted
much
attention.
Disulfide
good
reductive
responsiveness
can
effectively
high
glutathione
(GSH)
levels
environment,
enabling
precise
delivery.
further
enhance
targeting
accelerate
release,
are
often
combined
with
pH-responsive
nanocarriers
highly
expressed
ligands
cells
construct
systems.
connect
molecules
polymer
system,
as
well
between
different
carrier
molecules.
This
article
summarized
systems
(DDS)
that
researchers
constructed
years
bond
microenvironment,
cleavage-triggering
conditions,
various
loading
strategies,
design.
In
this
review,
we
also
discuss
controlled
release
mechanisms
these
DDS
clinical
applicability
challenges
faced
translation.
Keywords:
bond,
systems,
GSH/ROS
International Journal of Nanomedicine,
Год журнала:
2024,
Номер
Volume 19, С. 945 - 964
Опубликована: Янв. 1, 2024
Abstract:
The
active
metabolite
of
irinotecan
(CPT-11),
7-ethyl-10-hydroxycamptothecin
(SN38),
is
100–
1000
times
more
than
CPT-11
and
has
shown
inhibitory
effects
on
a
range
cancer
cells,
including
those
from
the
rectal,
small
cell
lung,
breast,
esophageal,
uterine,
ovarian
malignancies.
Despite
SN38's
potent
anticancer
properties,
its
hydrophobicity
pH
instability
have
caused
substantial
side
activity
loss,
which
make
it
difficult
to
use
in
clinical
settings.
To
solve
above
problems,
construction
SN38-based
drug
delivery
systems
one
most
feasible
methods
improve
solubility,
enhance
stability,
increase
targeting
ability,
bioavailability,
therapeutic
efficacy
reduce
adverse
reactions.
Therefore,
based
mechanism
systems,
this
paper
reviews
SN38
polymeric
micelles,
liposomal
nanoparticles,
protein
conjugated
targeted
by
aptamers
ligands,
antibody-drug
couplings,
magnetic
targeting,
photosensitive
redox-sensitive
multi-stimulus-responsive
co-loaded
systems.
focus
review
nanocarrier-based
We
hope
provide
reference
for
translation
application
novel
medications.
Keywords:
SN38,
system,
Combinatorial Chemistry & High Throughput Screening,
Год журнала:
2024,
Номер
27(11), С. 1611 - 1628
Опубликована: Янв. 12, 2024
Osteoporosis
(OP)
is
an
age-related
skeletal
disease.
Kaempferol
can
regulate
bone
mesenchymal
stem
cells
(BMSCs)
osteogenesis
to
improve
OP,
but
its
mechanism
related
disulfidptosis,
a
newly
discovered
cell
death
mechanism,
remains
unclear.
Frontiers in Chemistry,
Год журнала:
2024,
Номер
12
Опубликована: Март 27, 2024
Triple-negative
breast
cancer
(TNBC)
is
an
aggressive
subtype
of
still
lacking
effective
treatment
options.
Chemotherapy
in
combination
with
immunotherapy
can
restrict
tumor
progression
and
repolarize
the
microenvironment
towards
anti-tumor
milieu,
improving
clinical
outcome
TNBC
patients.
The
chemotherapeutic
drug
paclitaxel
has
been
shown
to
induce
immunogenic
cell
death
(ICD),
whereas
inhibitors
indoleamine
2,3-
dioxygenase
1
(IDO1)
enzyme,
whose
expression
shared
immune
regulatory
cells,
have
revealed
enhance
response.
However,
poor
bioavailability
pharmacokinetics,
off-target
effects
hurdles
achieving
therapeutic
concentrations
at
target
tissue
often
limit
effectiveness
therapies.
This
work
describes
development
novel
biomimetic
carrier-free
nanobinders
(NBs)
loaded
both
IDO1
inhibitor
NLG919
form
bioresponsive
prodrugs.
A
fine
tuning
preparation
conditions
allowed
identify
NB@5
as
most
suitable
nanoformulation
terms
reproducibility,
stability
vitro
effectiveness.
Our
data
show
that
effectively
binds
HSA
cell-free
experiments,
demonstrating
its
protective
role
controlled
release
drugs
suggesting
potential
exploit
protein
endogenous
vehicle
for
targeted
delivery
site.
study
successfully
proves
encapsulated
within
NBs
are
preferentially
released
under
altered
redox
commonly
found
microenvironment,
thereby
inducing
death,
promoting
ICD,
inhibiting
IDO1.
Molecules,
Год журнала:
2023,
Номер
28(13), С. 4931 - 4931
Опубликована: Июнь 22, 2023
As
a
camptothecin
derivative,
7-ethyl-10-hydroxycamptothecin
(SN38)
combats
cancer
by
inhibiting
topoisomerase
I.
SN38
is
one
of
the
most
active
compounds
among
derivatives.
In
addition,
also
theranostic
reagent
due
to
its
intrinsic
fluorescence.
However,
poor
water
solubility,
high
systemic
toxicity
and
limited
action
against
drug
resistance
metastasis
tumor
cells
indicates
that
there
great
space
for
structural
modification
SN38.
From
perspective
chemical
modification,
this
paper
summarizes
progress
in
improving
increasing
activity,
reducing
possessing
multifunction
analyzes
strategies
structure
provide
reference
development
based
on
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 12, 2024
Sunshinamide,
a
cyclodepsipeptide,
has
demonstrated
significant
potential
in
inhibiting
cancer
cell
proliferation.
Our
prior
research
established
the
total
synthesis
and
anticancer
properties
of
sunshinamide.
However,
deeper
understanding
structure–activity
relationship
(SAR)
sunshinamide
remained
imperative.
In
this
study,
we
aimed
to
elucidate
SAR
mechanistic
insights
underlying
action,
both
vitro
vivo.
studies
confirm
crucial
roles
bicyclic-ring
disulfide
moiety
activity
recent
findings
unveil
that
targets
TrxR1,
leading
ROS
generation
ER-stress-mediated
apoptosis,
while
also
promoting
lipid
peroxidation
by
targeting
Gpx4,
rendering
cells
vulnerable
ferroptosis.
vivo,
experiments
effectiveness
reducing
tumor
growth
inducing
apoptosis
The
dual
efficacy
eliciting
ferroptosis
positions
it
as
promising
candidate
for
breast
therapy,
addressing
challenge
chemoresistance.
Frontiers in Pharmacology,
Год журнала:
2023,
Номер
14
Опубликована: Авг. 7, 2023
Pancreatic
cancer
is
a
common
malignancy
of
the
digestive
system.
With
high
degree
and
poor
prognosis,
it
called
“king
cancers.”
Currently,
Western
medicine
treats
pancreatic
mainly
by
surgical
resection,
radiotherapy,
chemotherapy.
However,
curative
effect
not
satisfactory.
The
application
Traditional
Chinese
Medicine
(TCM)
in
treatment
has
many
advantages
becoming
an
important
facet
comprehensive
clinical
treatment.
In
this
paper,
we
review
current
therapeutic
approaches
for
cancer.
We
also
protective
effects
shown
TCM
different
models
discuss
potential
molecular
mechanisms
these.