Nanomedicine,
Год журнала:
2025,
Номер
unknown, С. 1 - 13
Опубликована: Янв. 31, 2025
We
develop
and
evaluate
copper-based
metal-organic
frameworks
(Cu-MOFs)
incorporating
cromolyn
as
a
linker
to
enhance
structural
stability,
drug
delivery
efficiency,
therapeutic
potential,
particularly
for
breast
cancer
treatment.
Two
Cu-MOF
formulations
were
synthesized:
Cu-MOFs-BDC-DOX
(using
terephthalic
acid)
Cu-MOFs-CROMO-DOX
linker).
Characterization
was
performed
using
SEM/TEM
morphology,
FTIR,
XRD,
TGA
confirm
integrity.
Drug
encapsulation
efficiency
release
profiles
assessed,
followed
by
in
vitro
cytotoxicity,
cell
migration,
colony
formation
assays
MDA-MB-231
cells.
Both
demonstrated
high
(83-91%)
sustained
over
48
h
at
pH
7.4.
exhibited
superior
cytotoxicity
with
an
IC50
of
0.88
±
0.07
µM
compared
7.1
0.11
Cu-MOFs-BDC-DOX.
inhibit
migration
dose-dependent
manner.
The
formulation
enhanced
outperforming
its
counterpart
targeting
This
study
highlights
the
promise
MOF-based
nanocarriers
overcoming
limitations
conventional
chemotherapy,
offering
pathway
more
effective
targeted
treatments
reduced
side
effects.
Abstract
Triple-negative
breast
cancer
(TNBC)
poses
a
significant
challenge
in
treatment
due
to
the
emergence
of
drug
resistance
standard
chemotherapeutics,
along
with
associated
risks
non-targeted
tissues.
This
study
is
dedicated
developing
nanoparticle
delivery
system
utilizing
PLGA-PEG
nanoparticles
(NP)
integration
A6
peptide
(NPA6)
as
specific
targeting
ligand
for
TNBC.
Encapsulating
Doxorubicin
(DOX)
and
antisense-miR-21
(AM21),
these
are
designed
counter
vitro
vivo.
Characterized
by
an
average
size
103.5
(±8.1)
nm
remarkable
DOX
encapsulation
efficiency,
have
been
successfully
engineered.
Results
demonstrate
that
NPA6.DOX.AM21
effectively
mitigates
resistance,
displaying
significantly
decreased
doxorubicin
IC
50
opposed
free
(2.5
µM
vs
25.7µMrespectively,
p<0.01).
In
mice
models,
peptide-incorporated
formulation
(NPA6.DOX,
NPA6.DOX.AM21)
exhibits
substantial
tumour
reduction
increased
concentration
within
tumours,
all
while
minimizing
non-specific
exposure
compared
non-A6
formulations
(NPDOX,
FREE
DOX)
treatments.
innovative
PLGA-PEG-A6
complex
loaded
AM21
showcases
superior
efficacy
surmounting
cell
line,
progression,
decreasing
distribution
organs
mice.
These
results
hold
promise
enhanced
combat
against
precise
chemotherapy,
hence
potentially
improving
patient
outcomes
survival
rates.
Graphical
abstact
Figure
abstract
study.
Fron
left
right,
development
followed
characterization
vivo
reduce
target
triple
negative
(TNBC).
PLGA:
polylactic-co-glycolic
acid,
PEG:
polyethylene
glycol,
A6:
peptide,
DOX:
Doxorubicin,
AM21:
antisense-microRNA
-21
Highlights
The
conjugated
co-loaded
anti-miRNA21
(NPA6.DOX.AM21)
was
fabricated
99.8
-
diameter
PDI
0.2
high
drugs
efficiency.
death,
reduced
MDA
MB-231
resistant
cells,
dose.
targeted
TNBC
size,
tumor
less
accumulation
off-target
organs,
comparison
control
model.
Nanomedicine,
Год журнала:
2025,
Номер
unknown, С. 1 - 13
Опубликована: Янв. 31, 2025
We
develop
and
evaluate
copper-based
metal-organic
frameworks
(Cu-MOFs)
incorporating
cromolyn
as
a
linker
to
enhance
structural
stability,
drug
delivery
efficiency,
therapeutic
potential,
particularly
for
breast
cancer
treatment.
Two
Cu-MOF
formulations
were
synthesized:
Cu-MOFs-BDC-DOX
(using
terephthalic
acid)
Cu-MOFs-CROMO-DOX
linker).
Characterization
was
performed
using
SEM/TEM
morphology,
FTIR,
XRD,
TGA
confirm
integrity.
Drug
encapsulation
efficiency
release
profiles
assessed,
followed
by
in
vitro
cytotoxicity,
cell
migration,
colony
formation
assays
MDA-MB-231
cells.
Both
demonstrated
high
(83-91%)
sustained
over
48
h
at
pH
7.4.
exhibited
superior
cytotoxicity
with
an
IC50
of
0.88
±
0.07
µM
compared
7.1
0.11
Cu-MOFs-BDC-DOX.
inhibit
migration
dose-dependent
manner.
The
formulation
enhanced
outperforming
its
counterpart
targeting
This
study
highlights
the
promise
MOF-based
nanocarriers
overcoming
limitations
conventional
chemotherapy,
offering
pathway
more
effective
targeted
treatments
reduced
side
effects.
