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POTENCIACIÓN
DE
LA
ACTIVIDAD
ANTITUMORAL
DE
DOXORRUBICINA…

ABSTRACT

Improvement
of
the
antitumor
activity
of
doxorubicin
by
the
use
of
magnetic

nanoplatforms

The
introduction
of
magnetic
nanoplatforms
in
the
cancer
arena
is
intended
to

optimize
the
accumulation
of
the
drug
dose
into
the
tumor
interstitium
with
the

help
of
a
magnetic
gradient.
As
a
result,
the
chemotherapeutic
agent
may
exhibit
an

enhanced
anticancer
efficacy
and
a
negligible
systemic
toxicity.
In
these
contexts,

we
have
developed
a
reproducible
methodology
for
the
design
of
magnetite/poly

(e-­-caprolactone)
core/shell
nanoparticles.
A
detailed
physicochemical

characterization
of
these
nanocomposites
suggested
that
their
heterogeneous

structure
allows
their
use
in
drug
delivery,
thanks
to
an
excellent
responsiveness
to

magnetic
gradients.
In
vitro
heating
characteristics
(hyperthermia
inducing

capability)
of
the
core/shell
nanoparticles
were
investigated
in
a
high
frequency

alternating
magnetic
gradient.
Blood
compatibility
of
the
nanoformulation
was

defined
in
vitro.
Finally,
this
nanodevice
was
used
to
enhance
the
intravenous

delivery
of
the
anticancer
agent
doxorubicin
to
the
tumor
tissue.
The

nanocomposites
were
characterized
by
an
adequate
doxorubicin
loading,
a

significant
magnetic
susceptibility,
and
a
low
burst
drug
release.
When
injected
to

the
EMT6
subcutaneous
mice
tumor
model,
these
doxorubicin-­-loaded
core/shell

nanoparticles
were
magnetically
guided,
and
they
displayed
considerably
greater

anticancer
activity
than
the
other
anticancer
treatments
(i.e.,
doxorubicin-­-loaded

nanocomposites
non-­-magnetically
guided,
or
doxorubicin
free
in
solution).
Thus,
the

here-­-described
stimuli-­-sensitive
nanomedicine
possesses
important
characteristics

for
effective
therapy
of
cancer.

Keywords:
Cancer;
Drug
delivery;
Hyperthermia;
Magnetic
nanoparticles;

Nanocomposites.

1.
INTRODUCCIÓN

La
necesidad
de
encontrar
tratamientos
quimioterápicos
eficaces
ha
hecho

que
se
incrementen
las
líneas
de
investigación
en
esta
materia.
Esto
ha
permitido

un
mayor
conocimiento
de
los
orígenes
moleculares
del
cáncer,
con
la
consiguiente

identificación
de
novedosas
aproximaciones
terapéuticas
y
el
desarrollo
de
un

amplio
arsenal
de
moléculas
antitumorales.
Sin
embargo,
los
agentes

quimioterápicos
utilizados
en
clínica
suelen
presentar
importantes
limitaciones

que
determinan
el
habitual
fracaso
del
tratamiento
incluso
en
aquellos
tipos
de

cáncer
teóricamente
más
sensibles
(1).
Un
claro
ejemplo
lo
constituye
la
baja

respuesta
global
(˜
10
%)
alcanzada
con
la
utilización
de
5-­-fluorouracilo
en
el

tratamiento
del
cáncer
colorrectal
avanzado.
Además,
se
ha
descrito
que
la

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