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Increased cellular uptake of biocompatible superparamagnetic iron oxide nanoparticles into malignant cells by an external magnetic field.

Prijic S, Scancar J, Romih R, Cemazar M, Bregar VB, Znidarsic A, Sersa G - J. Membr. Biol. (2010)

Bottom Line: SPIONs, dispersed in 0.9% NaCl solution, resulted in a stable ferrofluid at physiological pH for several months.Exposure to neodymium-iron-boron magnets significantly increased the cellular uptake of SPIONs, predominantly into malignant cells.Their cellular uptake was dependent on the cell type, and their accumulation within the cells was dependent on the duration of exposure to an external magnetic field.

View Article: PubMed Central - PubMed

Affiliation: Kolektor Group, Nanotesla Institute, Stegne 29, 1521, Ljubljana, Slovenia. sara.prijic@nanotesla.si

ABSTRACT
Superparamagnetic iron oxide nanoparticles (SPIONs) are used as delivery systems for different therapeutics including nucleic acids for magnetofection-mediated gene therapy. The aim of our study was to evaluate physicochemical properties, biocompatibility, cellular uptake and trafficking pathways of the custom-synthesized SPIONs for their potential use in magnetofection. Custom-synthesized SPIONs were tested for size, shape, crystalline composition and magnetic behavior using a transmission electron microscope, X-ray diffractometer and magnetometer. SPIONs were dispersed in different aqueous media to obtain ferrofluids, which were tested for pH and stability using a pH meter and zetameter. Cytotoxicity was determined using the MTS and clonogenic assays. Cellular uptake and trafficking pathways were qualitatively evaluated by transmission electron microscopy and quantitatively by inductively coupled plasma atomic emission spectrometry. SPIONs were composed of an iron oxide core with a diameter of 8-9 nm, coated with a 2-nm-thick layer of silica. SPIONs, dispersed in 0.9% NaCl solution, resulted in a stable ferrofluid at physiological pH for several months. SPIONs were not cytotoxic in a broad range of concentrations and were readily internalized into different cells by endocytosis. Exposure to neodymium-iron-boron magnets significantly increased the cellular uptake of SPIONs, predominantly into malignant cells. The prepared SPIONs displayed adequate physicochemical and biomedical properties for potential use in magnetofection. Their cellular uptake was dependent on the cell type, and their accumulation within the cells was dependent on the duration of exposure to an external magnetic field.

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a Cytotoxicity to MeT-5A, L929 and SK-MEL-28 cells exposed to Nd–Fe–B magnets at different time intervals. Cytotoxicity of SPIONs to MeT-5A (b), L929 (c) and SK-MEL-28 (d) cells with additional exposure to Nd–Fe–B magnets for different time intervals. a When exposed to Nd–Fe–B magnets only, no statistically significant decrease in cell survival for all three cell lines was observed. b At longer exposures to Nd–Fe–B magnets (60 and 90 min), concentrations of SPIONs >25 μg/ml statistically significantly decreased survival of MeT-5A cells. c, d The highest concentrations of SPIONs (50 and 100 μg/ml) significantly decreased survival of L929 and SK-MEL-28 cells independently of the duration of exposure to an external magnetic field (P ≤ 0.05 vs. untreated control cells; for the purpose of clarity, we omitted asterisks representing statistically significant differences)
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Fig6: a Cytotoxicity to MeT-5A, L929 and SK-MEL-28 cells exposed to Nd–Fe–B magnets at different time intervals. Cytotoxicity of SPIONs to MeT-5A (b), L929 (c) and SK-MEL-28 (d) cells with additional exposure to Nd–Fe–B magnets for different time intervals. a When exposed to Nd–Fe–B magnets only, no statistically significant decrease in cell survival for all three cell lines was observed. b At longer exposures to Nd–Fe–B magnets (60 and 90 min), concentrations of SPIONs >25 μg/ml statistically significantly decreased survival of MeT-5A cells. c, d The highest concentrations of SPIONs (50 and 100 μg/ml) significantly decreased survival of L929 and SK-MEL-28 cells independently of the duration of exposure to an external magnetic field (P ≤ 0.05 vs. untreated control cells; for the purpose of clarity, we omitted asterisks representing statistically significant differences)

Mentions: In order to determine the potential cytotoxic effect of Nd–Fe–B magnets, the viability of all three cell lines was assessed by the MTS assay at different durations of exposure to an external magnetic field. There was no statistically significant decrease in survival of all three cell lines compared to the unexposed control group at all time intervals (Fig. 6).Fig. 6


Increased cellular uptake of biocompatible superparamagnetic iron oxide nanoparticles into malignant cells by an external magnetic field.

Prijic S, Scancar J, Romih R, Cemazar M, Bregar VB, Znidarsic A, Sersa G - J. Membr. Biol. (2010)

a Cytotoxicity to MeT-5A, L929 and SK-MEL-28 cells exposed to Nd–Fe–B magnets at different time intervals. Cytotoxicity of SPIONs to MeT-5A (b), L929 (c) and SK-MEL-28 (d) cells with additional exposure to Nd–Fe–B magnets for different time intervals. a When exposed to Nd–Fe–B magnets only, no statistically significant decrease in cell survival for all three cell lines was observed. b At longer exposures to Nd–Fe–B magnets (60 and 90 min), concentrations of SPIONs >25 μg/ml statistically significantly decreased survival of MeT-5A cells. c, d The highest concentrations of SPIONs (50 and 100 μg/ml) significantly decreased survival of L929 and SK-MEL-28 cells independently of the duration of exposure to an external magnetic field (P ≤ 0.05 vs. untreated control cells; for the purpose of clarity, we omitted asterisks representing statistically significant differences)
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2914263&req=5

Fig6: a Cytotoxicity to MeT-5A, L929 and SK-MEL-28 cells exposed to Nd–Fe–B magnets at different time intervals. Cytotoxicity of SPIONs to MeT-5A (b), L929 (c) and SK-MEL-28 (d) cells with additional exposure to Nd–Fe–B magnets for different time intervals. a When exposed to Nd–Fe–B magnets only, no statistically significant decrease in cell survival for all three cell lines was observed. b At longer exposures to Nd–Fe–B magnets (60 and 90 min), concentrations of SPIONs >25 μg/ml statistically significantly decreased survival of MeT-5A cells. c, d The highest concentrations of SPIONs (50 and 100 μg/ml) significantly decreased survival of L929 and SK-MEL-28 cells independently of the duration of exposure to an external magnetic field (P ≤ 0.05 vs. untreated control cells; for the purpose of clarity, we omitted asterisks representing statistically significant differences)
Mentions: In order to determine the potential cytotoxic effect of Nd–Fe–B magnets, the viability of all three cell lines was assessed by the MTS assay at different durations of exposure to an external magnetic field. There was no statistically significant decrease in survival of all three cell lines compared to the unexposed control group at all time intervals (Fig. 6).Fig. 6

Bottom Line: SPIONs, dispersed in 0.9% NaCl solution, resulted in a stable ferrofluid at physiological pH for several months.Exposure to neodymium-iron-boron magnets significantly increased the cellular uptake of SPIONs, predominantly into malignant cells.Their cellular uptake was dependent on the cell type, and their accumulation within the cells was dependent on the duration of exposure to an external magnetic field.

View Article: PubMed Central - PubMed

Affiliation: Kolektor Group, Nanotesla Institute, Stegne 29, 1521, Ljubljana, Slovenia. sara.prijic@nanotesla.si

ABSTRACT
Superparamagnetic iron oxide nanoparticles (SPIONs) are used as delivery systems for different therapeutics including nucleic acids for magnetofection-mediated gene therapy. The aim of our study was to evaluate physicochemical properties, biocompatibility, cellular uptake and trafficking pathways of the custom-synthesized SPIONs for their potential use in magnetofection. Custom-synthesized SPIONs were tested for size, shape, crystalline composition and magnetic behavior using a transmission electron microscope, X-ray diffractometer and magnetometer. SPIONs were dispersed in different aqueous media to obtain ferrofluids, which were tested for pH and stability using a pH meter and zetameter. Cytotoxicity was determined using the MTS and clonogenic assays. Cellular uptake and trafficking pathways were qualitatively evaluated by transmission electron microscopy and quantitatively by inductively coupled plasma atomic emission spectrometry. SPIONs were composed of an iron oxide core with a diameter of 8-9 nm, coated with a 2-nm-thick layer of silica. SPIONs, dispersed in 0.9% NaCl solution, resulted in a stable ferrofluid at physiological pH for several months. SPIONs were not cytotoxic in a broad range of concentrations and were readily internalized into different cells by endocytosis. Exposure to neodymium-iron-boron magnets significantly increased the cellular uptake of SPIONs, predominantly into malignant cells. The prepared SPIONs displayed adequate physicochemical and biomedical properties for potential use in magnetofection. Their cellular uptake was dependent on the cell type, and their accumulation within the cells was dependent on the duration of exposure to an external magnetic field.

Show MeSH
Related in: MedlinePlus