This study concerns the development of folic acid (FA)-functionalized
iron oxide condensed colloidal magnetic clusters for a more selective
delivery of doxorubicin (DOX) to tumor cancer cells overexpressing
the folate receptor. Alginate-coated condensed magnetic nanoparticles
(co-MIONs) were synthesized via an alkaline precipitation method of
an iron precursor in the presence of sodium alginate. Poly(ethylene
glycol) (OH-PEG-NH2) was conjugated to the carboxylic acid
end group of alginate and folic acid (FA) was conjugated to the hydroxyl
terminal group of PEG to produce folate-functionalized, pegylated
co-MIONS (Mag-Alg-PEG-FA). The physicochemical properties of nanoparticles
were fully characterized. DOX was loaded on the nanoparticles, and
the cellular uptake and anticancer efficacy of the nanoparticles were
examined in cancer cell lines expressing and not expressing the folate
receptor. The biocompatibility of the carrier (blank nanoparticles)
was also evaluated by cytocompatibility and hemocompatibility experiments.
The nanoparticles exhibited sustained DOX release in aqueous buffers
and biorelevant media, which was responsive to pH and external alternating
current magnetic fields. The effect of the magnetic field on DOX percentage
release appeared to be independent of the timing (onset time) of magnetic
field application, providing flexibility to the magnetic control of
drug release from the nanoparticles. The blank nanoparticles were
not cytotoxic and did not cause hemolysis. The DOX-loaded and FA-functionalized
nanoparticles exhibited increased uptake and caused increased apoptosis
and cytotoxicity against the MDA-MB-231 cell line, expressing the
folate receptor, compared to the MCF-7 cell line, not expressing the
folate receptor. The application of a 0.5 T magnetic field during
incubation of the nanoparticles with the cancer cells increased the
cellular uptake and cytotoxicity of the nanoparticles. The obtained
results indicate the potential of the folate-functionalized, pegylated
co-MIONS for a more efficacious DOX delivery to cancer cells of solid
tumors.