The Interplay between Fe3O4 Superparamagnetic Nanoparticles, Sodium Butyrate, and Folic Acid for Intracellular Transport

Abstract

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.

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

“…Therefore, an important issue for GBM treatment is the development of a suitable carrier to protect and deliver a specific drug such as TMZ. 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 , 11 , 12 , 13 ] and, in particular, organic functionalized Fe 3 O 4 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 ]. Recently, 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 , 21 , 22 , 23 , 24 ].…”

Novel strategies to reverse chemoresistance in colorectal cancer

“…Other multifunctional codelivery systems, like mesoporous silica‐coated gold nanorods (GNRs/mSiO2) loaded with DOX, conjugated with pH‐responsive poly‐histidine (PHIS), and covered with d‐α‐tocopherol polyethylene glycol 1000 succinate (TPGS) was discovered to increase the drug accumulation and promote photothermal conversion in tumor resistant CRC cells and exert better anticancer effects in SW620/Ad300 xenograft mice without observed systemic toxicity compared with other chemotherapy or photothermal therapy alone 126 . Combination use of sodium butyrate and Fe3O4 magnetic nanoparticles (MNPs), coated with folic acid (FA) and polyethylene glycol (PEG) (FA‐PEG@MNPs), could decrease cell viability and increase FA‐PEG@MNPs intracellular uptake in Lovo cells, which indicated that the combined use may exert MDR resistance reversal effect in CRC 127 . Due to the multiple advantages of nanocarriers, recently, more studies are focusing on nanocarriers and trying to find different ways to overcome chemoresistance 128,129 …”

“… 126 Combination use of sodium butyrate and Fe3O4 magnetic nanoparticles (MNPs), coated with folic acid (FA) and polyethylene glycol (PEG) (FA‐PEG@MNPs), could decrease cell viability and increase FA‐PEG@MNPs intracellular uptake in Lovo cells, which indicated that the combined use may exert MDR resistance reversal effect in CRC. 127 Due to the multiple advantages of nanocarriers, recently, more studies are focusing on nanocarriers and trying to find different ways to overcome chemoresistance. 128 , 129 …”

Transmission Electron Microscopy as a Powerful Tool to Investigate the Interaction of Nanoparticles with Subcellular Structures

“…Despite the high resolution (3–20 nm), imaging is restricted to the surface of the sample. For this reason, SEM has mostly been used in nanomedical research to characterize the spatial relationships between nanoparticulates and the cell surface with particular reference to the internalization process and cell shape modification [ 25 , 26 , 27 , 28 ] although field emission SEM (using a high energy beam of electrons) has allowed the visualization of nanoparticles also in the endosomal compartment [ 29 ].…”