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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.

SUBMITTER: Cambria MT

PROVIDER: S-EPMC7697628 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Cambria Maria Teresa MT Villaggio Giusy G Laudani Samuele S Pulvirenti Luca L Federico Concetta C Saccone Salvatore S Condorelli Guglielmo Guido GG Sinatra Fulvia F

International journal of molecular sciences 20201111 22

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 effe ...[more]

PMID: 33187164

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Project description:In this paper, we present the obtaining of Fe3O4-PAA-(HP-γ-CDs) ferrimagnetic nanobioconjugates (PAA: polyacrylic acid, HP-γ-CDs: hydroxypropyl gamma-cyclodextrins) in a hybrid core-shell biostructure (core: inorganic Fe3O4 nanoparticles, and shell: organic PAA-(HP-γ-CDs)) and their use in superparamagnetic hyperthermia without cellular toxicity and with increased efficacy for future alternative cancer therapy. In order to design the optimal experimental conditions for obtaining nanobioconjugates and then superparamagnetic hyperthermia (SPMHT), we used molecular docking simulation and computational assessment of the maximum specific loss power (SLP) that led to nanoparticles' heating. The nanoparticles and nanobioconjugates obtained were studied and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transformed-infrared spectroscopy (FT-IR), dynamic light scattering (DLS), and magnetic measurements (MMs). The cell viability of the nanoparticles and nanobioconjugates was assessed by means of the MTT assay using human immortalized keratinocytes (HaCaT) as an in vitro model. Superparamagnetic hyperthermia with nanoparticles and nanobioconjugates was obtained experimentally in a magnetic field of 15.92 kA/m and frequency of 312.2 kHz for the magnetic nanoparticle core with a (average) diameter of 15.8 nm, which resulted in the maximum hyperthermic effect that led to a temperature of ~42.5 °C necessary in the therapy of tumors in a short time so as not to affect healthy tissues. The biological screening of Fe3O4-PAA nanoparticles and PAA-(HP-γ-CDs) nanobioconjugates showed no cytotoxic effect on HaCaT cells for a time interval of 24 h, both under standard (37 °C) and hyperthermia conditions (42.5 °C). Thus, Fe3O4-PA-(HP-γ-CDs) ferrimagnetic nanobioconjugates can be used successfully in superparamagnetic hyperthermia without toxicity and with increased efficiency due to the small layer thickness of the PAA-(HP-γ-CDs) shell, which is suitable in this alternative therapeutic technique.

Project description:Herein, we report on developing a facile synthetic route for reusable nanocatalysts based on a combination of the supermagnetic properties of magnetite with the unique optical and catalytic properties of noble metal hybrid nanomaterials. We compare two different synthetic methods, to find out which is best from synthetic and application points of view, for the synthesis of Fe3O4 and Fe3O4@M (M = Ag or Au) core-shell hybrid nanostructures. The two different single-step synthetic methods are: thermal decomposition and hydrothermal. The structural, morphological and magnetic properties of the obtained Fe3O4 and Fe3O4@M nanoparticles were characterized by various techniques. XRD of the Fe3O4 nanoparticles exhibited sharp and strong diffraction peaks, confirming the highly crystalline structure of the Fe3O4 particles synthesized by the hydrothermal method, while broad and weak peaks were observed on using the thermal decomposition method. Both Fe3O4@Ag and Fe3O4@Au core-shells obtained by the hydrothermal method showed the reflection planes of Fe3O4 and additional planes of Ag or Au. But on the formation of Fe3O4@Ag/Au by the thermal decomposition method the peak for Fe3O4 disappeared and only the diffraction peaks of Ag or Au appeared. According to TEM analysis there was a broad particle-size distribution, random near-spherical shapes and slight particle agglomeration for Fe3O4 synthesized by the thermal decomposition method. However, there was a moderate size distribution, spherical shapes and well-dispersed particles without large aggregations for the hydrothermal method. TEM images of the synthesized nanoparticles by the two methods used showed a pronounced difference in both size and morphological shape. The catalytic performance of the synthesized nanoparticles was examined for the reduction of Congo red dye in the presence of NaBH4. The Fe3O4 nanocatalyst maintained its catalytic activity for only one cycle. In the cases of Fe3O4@Au and Fe3O4@Ag, the catalytic activity was conserved for four and ten successive cycles, respectively. Based on the obtained results, it was concluded that the hydrothermal synthesis of Fe3O4, Fe3O4@Ag and Fe3O4@Au nanostructures is highly recommended due to their selectivity and merits.

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

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The Interplay between Fe<sub>3</sub>O<sub>4</sub> Superparamagnetic Nanoparticles, Sodium Butyrate, and Folic Acid for Intracellular Transport.

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