Abstract
A nanometric hybrid system consisting of a Fe3O4 magnetic nanoparticles modified through the growth of Fe-based Metal-organic frameworks of the MIL (Materials Institute Lavoiser) was developed. The obtained system retains both the nanometer dimensions and the magnetic properties of the Fe3O4 nanoparticles and possesses increased the loading capability due to the highly porous Fe-MIL. It was tested to load, carry and release temozolomide (TMZ) for the treatment of glioblastoma multiforme one of the most aggressive and deadly human cancers. The chemical characterization of the hybrid system was performed through various complementary techniques: X-ray-diffraction, thermogravimetric analysis, FT-IR and X-ray photoelectron spectroscopies. The nanomaterial showed low toxicity and an increased adsorption capacity compared to bare Fe3O4 magnetic nanoparticles (MNPs). It can load about 12 mg/g of TMZ and carry the drug into A172 cells without degradation. Our experimental data confirm that, after 48 h of treatment, the TMZ-loaded hybrid nanoparticles (15 and 20 μg/mL) suppressed human glioblastoma cell viability much more effectively than the free drug. Finally, we found that the internalization of the MIL-modified system is more evident than bare MNPs at all the used concentrations both in the cytoplasm and in the nucleus suggesting that it can be capable of overcoming the blood-brain barrier and targeting brain tumors. In conclusion, these results indicate that this combined nanoparticle represents a highly promising drug delivery system for TMZ targeting into cancer cells.
Highlights
Glioblastoma multiforme (GBM) is one of the most common, deadly and difficult to treat brain tumors [1]
We found that the internalization of the MIL-modified system is more evident than bare magnetic nanoparticles (MNPs) at all the used concentrations both in the cytoplasm and in the nucleus suggesting that it can be capable of overcoming the blood-brain barrier and targeting brain tumors
Metal-Organic Frameworks (MOFs) coordination polymers consisting of metal nodes and polydentate organic linkers organized in open porous structures [18,19] and, among them, MILs (Materials Institute Lavoiser) an MOF subclass constituted by trivalent transition metals and bi- or tri-carboxylic ligands, showed great potentiality for biomedical applications either as pure crystals or as composite materials, because of their biocompatibility and capability of loading molecules in their porous structure [20–24]
Summary
Glioblastoma multiforme (GBM) is one of the most common, deadly and difficult to treat brain tumors [1]. In this regard nanostructured systems such as liposomes, polymeric and functionalized inorganic nanoparticles have shown promising results in the delivery of active drugs to the brain [10–13] and, in particular, organic functionalized Fe3O4 nanoparticles have attracted increasing attention [14,15] because of the combination of the magnetic properties and biocompatibility of the iron core with the versatility of the functionalization shells [16,17]. Some paper reported on the possibility of combining magnetic nanoparticles with MILs structures either as composite materials made of MILs crystals decorated or loaded with magnetic Fe3O4 nanoparticles [25–28] or core-shell systems in which an Fe3O4 core is covered with a MIL shell [29–35] In both cases typically particles sizes ranged from 200–500 nm.
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