Bcl-2 knockdown by multifunctional lipid nanoparticle and its influence in apoptosis pathway regarding cutaneous melanoma: in vitro and ex vivo studies.
Abstract
Multifunctional
therapies
have
emerged
as
innovative
strategies
in
cancer
treatment.
In
this
research
article,
we
proposed
a
nanostructured
lipid
carrier
(NLC)
designed
for
the
topical
treatment
of
cutaneous
melanoma,
which
simultaneously
delivers
5-FU
and
Bcl-2
siRNA.
The
characterized
nanoparticles
exhibited
diameter
259
±
9
nm
polydispersion
index
0.2,
indicating
uniform
size
distribution.
NLCs
were
primarily
localized
epidermis,
effectively
minimizing
systemic
release
across
skin
layers.
ex
vivo
model
revealed
formation
protective
film,
decreasing
desquamation
process
stratum
corneum
which
can
be
associated
to
an
effect
increasing
permeation.
In
vitro
assays
demonstrated
that
A375
melanoma
cells
higher
sensitivity
compared
non-cancerous
cells,
reflecting
expected
difference
their
metabolic
rates.
uptake
NLC
by
reached
approximately
90%
within
4
hours.
efficacy
knockdown
was
thoroughly
assessed
using
ELISA,
Western
blot,
qRT-PCR
analyses,
revealing
significant
synergistic
action
formulation
containing
siRNA
(at
low
concentration
--100
pM).
Notably,
silencing
mRNA
also
impacted
other
members
protein
family,
including
Mcl-1,
Bcl-xl,
BAX,
BAK.
observed
modulation
these
proteins
strongly
indicated
activation
apoptosis
pathway,
suggesting
successful
inhibition
growth
prevention
its
in
spread.
Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown
Published: June 4, 2024
Language: Английский