Increased Cellular Uptake of Biocompatible Superparamagnetic Iron Oxide Nanoparticles into Malignant Cells by an External Magnetic Field

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.

Differences in Magnetic Particle Uptake by CNS Neuroglial Subclasses: Implications for Neural Tissue Engineering

“…Most work to date evaluating cellular MP uptake and handling has utilized cell lines [34][35][36][37][38]. This risks chronic contamination by mycoplasma -such 'cryptic' contamination can alter cell structure, metabolism and growth, all of which can impact the interpretation of data [42].…”

Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers

“…Accumulation of SPIONs within malignant cells was found to be dependent on duration of exposure to the external magnetic field. 61 …”

Iron oxide nanoparticles and magnetic field exposure promote functional recovery by attenuating free radical-induced damage in rats with spinal cord transection

“…Cytotoxicity assay GBM-U87 cells were treated with different concentrations of IONPs (10,25,50, and 100 µg/mL). In comparison with the controls, treated cells did not show any significant difference in survival (Figure 2A Figure 2C).…”

“…24 Retention and accumulation of IONPs in cells can be enhanced by an external magnetic field (MF), providing mechanical tensile forces that may cause axonal sprouting. 19,25 An MF can also magnetize nanoparticles such that their beneficial effects can be focused to the site of injury. An MF can noninvasively create electric fields in deep underlying structures, thereby modulating oxidative stress, apoptosis, release of neurotransmitters, secretion of neurotrophic factors, and axonal growth.…”