Effect of cell media on polymer coated superparamagnetic iron oxide nanoparticles (SPIONs): Colloidal stability, cytotoxicity, and cellular uptake studies (original) (raw)
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Cell toxicity of superparamagnetic iron oxide nanoparticles
Journal of colloid and interface science, 2009
The performance of nanoparticles for biomedical applications is often assessed by their narrow size distribution, suitable magnetic saturation and low toxicity effects. In this work, superparamagnetic iron oxide nanoparticles (SPIONs) with different size, shape and saturation magnetization levels were synthesized via a co-precipitation technique using ferrous salts with a Fe 3+ /Fe 2+ mole ratio equal to 2. A parametric study is conducted, based on a uniform design-of-experiments methodology and a critical polymer/iron mass ratio (r-ratio) for obtaining SPION with narrow size distribution, suitable magnetic saturation, and optimum biocompatibility is identified. Polyvinyl alcohol (PVA) has been used as the nanoparticle coating material, owing to its low toxicity. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay is used to investigate the cell biocompatibility/toxicity effects of the samples. From the MTT assay results, it is observed that the biocompatibility of the nanoparticles, based on cell viabilities, can be enhanced by increasing the r-ratio, regardless of the stirring rate. This effect is mainly due to the growth of the particle hydrodynamic size, causing lower cell toxicity effects.
ScienceAsia, 2019
Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely studied in biomedical applications such as bioimaging through magnetic resonance imaging and drug delivery. The successful uses of SPIONs depend on nanoparticles stability in biological environment and their interactions with cells. Hence these two factors are crucial for improvement of nanoparticle design in these applications. In this work, SPIONs were synthesized with silica (S-SPIONs) and amine (A-SPIONs) surface modifications providing hydroxyl and amine functionalities, respectively. The colloidal stabilities of SPIONs were evaluated as hydrodynamic size in different biological relevance media. The results showed that bare SPIONs were unstable and highly aggregated when exposed to cell culture media. Coating with silica and amine could effectively stabilized the nanoparticles as evidenced by reduction of hydrodynamic diameters. In addition to surface modification, supplementation of serum proteins to cell culture media also reduced the aggregations. Furthermore, both S-SPIONs and A-SPIONs showed no cytotoxicity effect on human breast cancer cells (MCF-7) with cell viability remained over 80%. Hence this study showed the role of surface modification of bare SPIONs with silica and amine functionalization and serum supplement to stabilize nanoparticle stability in biological environment. These two surface coating SPIONs were not only non-toxic to the cells, but also have surface functionalities that could be further conjugated with desired biomolecules for more specific targeting especially in cancer targeting for diagnosis or therapeutic applications.
The Journal of Membrane Biology, 2010
Superparamagnetic iron oxide nanoparticles (SPIONs) are used as delivery systems for different therapeutics including nucleic acids for magnetofectionmediated 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. Customsynthesized 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.
International Journal of Molecular Sciences, 2016
The uptake and distribution of negatively charged superparamagnetic iron oxide (Fe 3 O 4) nanoparticles (SPIONs) in mouse embryonic fibroblasts NIH3T3, and magnetic resonance imaging (MRI) signal influenced by SPIONs injected into experimental animals, were visualized and investigated. Cellular uptake and distribution of the SPIONs in NIH3T3 after staining with Prussian Blue were investigated by a bright-field microscope equipped with digital color camera. SPIONs were localized in vesicles, mostly placed near the nucleus. Toxicity of SPION nanoparticles tested with cell viability assay (XTT) was estimated. The viability of NIH3T3 cells remains approximately 95% within 3-24 h of incubation, and only a slight decrease of viability was observed after 48 h of incubation. MRI studies on Wistar rats using a clinical 1.5 T MRI scanner were showing that SPIONs give a negative contrast in the MRI. The dynamic MRI measurements of the SPION clearance from the injection site shows that SPIONs slowly disappear from injection sites and only a low concentration of nanoparticles was completely eliminated within three weeks. No functionalized SPIONs accumulate in cells by endocytic mechanism, none accumulate in the nucleus, and none are toxic at a desirable concentration. Therefore, they could be used as a dual imaging agent: as contrast agents for MRI and for traditional optical biopsy by using Prussian Blue staining.
Toxicity assessment of superparamagnetic iron oxide nanoparticles in different tissues
Artificial Cells Nanomedicine and Biotechnology, 2020
Superparamagnetic iron oxide nanoparticles (SPIONs) have been employed in several biomedical applications where they facilitate both diagnostic and therapeutic aims. Although the potential benefits of SPIONs with different surface chemistry and conjugated targeting ligands/proteins are considerable, complicated interactions between these nanoparticles (NPs) and cells leading to toxic impacts could limit their clinical applications. Hence, elevation of our knowledge regarding the SPION-related toxicity is necessary. Here, the present review article will consider current studies and compare the potential toxic effect of SPIONs with or without identical surface chemistries on different cell lines. It centers on cellular and molecular mechanisms underlying toxicity of SPIONs. Likewise, emphasis is being dedicated for toxicity of SPIONs in various cell lines, in vitro and animal models, in vivo.
Chemical Engineering Journal, 2018
The response of cells to the exposure of nanomaterials is crucial for determining their safety in their multiple uses; however, the majority of the in vitro experiments use monolayered cell cultures instead of comparing the behavior of the cells in 3D, a more realistic environment. Here, we have analyzed how the exposed surface of the cells, as well as the environment where cells grow, can influence the interaction and uptake of superparamagnetic iron oxide nanoparticles (SPIONs). We exposed three different cell lines (MDAMB-231, HL60 and bEnd3), which grow at different environments, to increasing concentrations of SPIONs (0-150 µg•ml-1) and we evaluated parameters analyzing the morphological changes of the cell, iron uptake and cell viability. Results showed that upon exposure to SPIONs, cell viability and morphology are more affected when cells are growing in 3D systems, indicating that the increase of exposed surface area of the cells is a strong parameter to take in account when evaluating SPIONs or other materials or drugs. Our results clearly reinforce the use of more realistic environments, such as 3D, for the design of new drug delivery systems.
Cytotoxicity Studies of Superparamagnetic Iron Oxide Nanoparticles in Macrophage and Liver Cells
American Journal of Nanotechnology
Superparamagnetic Iron Oxide Nanoparticles (SPIONs) prepared by simplified coprecipitation were attractive as MRI contrast agents and drug carriers which could internally be manipulated under the influence of an external magnetic field and also cancer treatment due to additional hyperthermia effects. Problem statement: Macrophage and liver cells are potentially exposed to internal SPIONs, thus used for this cytotoxic tests for safety information of SPIONs. Approach: The SPIONs were physicochemically characterized by several instruments to ensure the production process. Cell viabilities, lipid peroxidation and nitric oxide produced after exposure to the SPIONs were conducted in normal macrophage and liver cells. Results: The approximately 15nm SPIONs produced had their structure confirmed by FTIR and X-ray diffraction and their magnetic properties probed by NMR. Macrophage and liver cells reacted differently to the SPIONs in dose-and time-dependent manners. Lipid peroxidation increased in macrophage cells, but not liver cells, after 24 h exposure to 100 µg mL −1 of SPIONs, but decreased after 72 h. Pro-inflammatory effect on macrophage cells induced by the SPIONs and measured as nitric oxide was not observed. Concentration of SPIONs up to 25 µg mL −1 did not alter cell function and morphology. Conclusion: SPIONs produced by our simplified co-precipitation are dose-dependent cytotoxic to macrophage and liver cells.