Synthesis of MIL-Modified Fe3O4 Magnetic Nanoparticles for Enhancing Uptake and Efficiency of Temozolomide in Glioblastoma Treatment

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 mu g/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.

Automated summary

We developed a nanometric hybrid system consisting of Fe3O4 magnetic nanoparticles modified through the growth of Fe-based Metal-organic frameworks, which showed increased loading capability and low toxicity compared to bare Fe3O4 magnetic nanoparticles. The system effectively loaded, carried, and released the drug TMZ for the treatment of glioblastoma multiforme and exhibited stronger inhibition of human glioblastoma cell viability. The internalization of the modified system was found to be more evident than bare nanoparticles, suggesting its potential in targeting brain tumors and overcoming the blood-brain barrier.