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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. [ABSTRACT FROM AUTHOR]

Combined treatments which use nanoparticles and drugs could be a synergistic strategy for the treatment of a variety of cancers to overcome drug resistance, low efficacy, and high-dose-induced systemic toxicity. In this study, the effects on human colon adenocarcinoma cells of surface modified Fe3O4 magnetic nanoparticles (MNPs) in combination with sodium butyrate (NaBu), added as a free formulation, were examined demonstrating that the co-delivery produced a cytotoxic effect on malignant cells. Two different MNP coatings were investigated: a simple polyethylene glycol (PEG) layer and a mixed folic acid (FA) and PEG layer. Our results demonstrated that MNPs with FA (FA-PEG@MNPs) have a better cellular uptake than the ones without FA (PEG@MNPs), probably due to the presence of folate that acts as an activator of folate receptors (FRs) expression. However, in the presence of NaBu, the difference between the two types of MNPs was reduced. These similar behaviors for both MNPs likely occurred because of the differentiation induced by butyrate that increases the uptake of ferromagnetic nanoparticles. Moreover, we observed a strong decrease of cell viability in a NaBu dose-dependent manner. Taking into account these results, the cooperation of multifunctional MNPs with NaBu, taking into consideration the particular cancer-cell properties, can be a valuable tool for future cancer treatment. [ABSTRACT FROM AUTHOR]

Brain and other nervous system cancers are the 10th leading cause of death worldwide. Genome instability, cell cycle deregulation, epigenetic mechanisms, cytoarchitecture disassembly, redox homeostasis as well as apoptosis are involved in carcinogenesis. A diet rich in fruits and vegetables is inversely related with the risk of developing cancer. Several studies report that cruciferous vegetables exhibited antiproliferative effects due to the multi-pharmacological functions of their secondary metabolites such as isothiocyanate sulforaphane deriving from the enzymatic hydrolysis of glucosinolates. We treated human astrocytoma 1321N1 cells for 24 h with different concentrations (0.5, 1.25 and 2.5% v/v ) of sulforaphane plus active myrosinase (Rapha Myr ® ) aqueous extract (10 mg/mL). Cell viability, DNA fragmentation, PARP-1 and γH2AX expression were examined to evaluate genotoxic effects of the treatment. Cell cycle progression, p53 and p21 expression, apoptosis, cytoskeleton morphology and cell migration were also investigated. In addition, global DNA methylation, DNMT1 mRNA levels and nuclear/mitochondrial sirtuins were studied as epigenetic biomarkers. Rapha Myr ® exhibited low antioxidant capability and exerted antiproliferative and genotoxic effects on 1321N1 cells by blocking the cell cycle, disarranging cytoskeleton structure and focal adhesions, decreasing the integrin α5 expression, renewing anoikis and modulating some important epigenetic pathways independently of the cellular p53 status. In addition, Rapha Myr ® suppresses the expression of the oncogenic p53 mutant protein. These findings promote Rapha Myr ® as a promising chemotherapeutic agent for integrated cancer therapy of human astrocytoma.