Synthesis and characterization of nano‐ and micron‐sized iron oxide and iron particles for biomedical applications

Margel, Shlomo; Lublin-Tennenbaum, Tammy; Gura, Sigalit; Tsubery, Merav Nadav; Akiva, Udi; Shpaisman, Nava; Galperin, Anna; Perlstein, Benny; Lapido, P.; Boguslavsky, Yonit; Goldshtein, Jenny

doi:10.1016/s0075-7535(06)32006-2

Cited by 12 publications

(8 citation statements)

References 56 publications

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“…The formed magnetic NPs were then washed from excess reagents with water using high gradient magnetic field (HGMF) technique. As soon as the washing step was completed, the column was removed from the magnetic field and the NPs were eluted by adding an aqueous bicarbonate buffer (BB, 0.1M, pH = 8.3) [ 66 ]. NIR core IO NPs were prepared similarly, by substituting the gelatin for gelatin covalently conjugated with NHS Cy7 to obtain NIR-IO NPs [ 20 ].…”

Section: Methodsmentioning

confidence: 99%

Bioactive magnetic near Infra-Red fluorescent core-shell iron oxide/human serum albumin nanoparticles for controlled release of growth factors for augmentation of human mesenchymal stem cell growth and differentiation

et al. 2015

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Background: Iron oxide (IO) nanoparticles (NPs) of sizes less than 50 nm are considered to be non-toxic, biodegradable and superparamagnetic. We have previously described the generation of IO NPs coated with Human Serum Albumin (HSA). HSA coating onto the IO NPs enables conjugation of the IO/HSA NPs to various biomolecules including proteins. Here we describe the preparation and characterization of narrow size distribution core-shell NIR fluorescent IO/HSA magnetic NPs conjugated covalently to Fibroblast Growth Factor 2 (FGF2) for biomedical applications. We examined the biological activity of the conjugated FGF2 on human bone marrow mesenchymal stem cells (hBM-MSCs). These multipotent cells can differentiate into bone, cartilage, hepatic, endothelial and neuronal cells and are being studied in clinical trials for treatment of various diseases. FGF2 enhances the proliferation of hBM-MSCs and promotes their differentiation toward neuronal, adipogenic and osteogenic lineages in vitro. Results: The NPs were characterized by transmission electron microscopy, dynamic light scattering, ultraviolet-visible spectroscopy and fluorescence spectroscopy. Covalent conjugation of the FGF2 to the IO/HSA NPs significantly stabilized this growth factor against various enzymes and inhibitors existing in serum and in tissue cultures. IO/HSA NPs conjugated to FGF2 were internalized into hBM-MSCs via endocytosis as confirmed by flow cytometry analysis and Prussian Blue staining. Conjugated FGF2 enhanced the proliferation and clonal expansion capacity of hBM-MSCs, as well as their adipogenic and osteogenic differentiation to a higher extent compared with the free growth factor. Free and conjugated FGF2 promoted the expression of neuronal marker Microtubule-Associated Protein 2 (MAP2) to a similar extent, but conjugated FGF2 was more effective than free FGF2 in promoting the expression of astrocyte marker Glial Fibrillary Acidic Protein (GFAP) in these cells. Conclusions: These results indicate that stabilization of FGF2 by conjugating the IO/HSA NPs can enhance the biological efficacy of FGF2 and its ability to promote hBM-MSC cell proliferation and trilineage differentiation. This new system may benefit future therapeutic use of hBM-MSCs.

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Section: Methodsmentioning

confidence: 99%

Bioactive magnetic near Infra-Red fluorescent core-shell iron oxide/human serum albumin nanoparticles for controlled release of growth factors for augmentation of human mesenchymal stem cell growth and differentiation

et al. 2015

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“…The functional groups of these coatings can then be used for the covalent binding of bioactive reagents such as drugs, proteins, antibodies and enzymes, to the surface of these maghemite nanoparticles. [24][25][26] Since maghemite nanoparticles have been shown to provide increased uptake in cancer cells versus normal cells, 27 and since human serum albumin (HSA) and polyethylene glycol (PEG) have been shown to increase the intake of MTX into cancer cells, 12,28,29 this study focuses on developing a methodology to bind MTX, a well-proven anti-tumor agent active in GBM, via HSA to the magnetic nanoparticles. The uptake of the drug-loaded particles and the efficacy of the drug-loaded particles versus the efficacy of the free drug were studied in vitro, followed by in vivo CED experiments to study the efficacy of distribution and clearance patterns of the nanoparticles in the brain.…”

Section: Introductionmentioning

confidence: 99%

Convection-enhanced delivery of methotrexate-loaded maghemite nanoparticles

Corem-Salkmon

Ram²,

Daniels³

et al. 2011

IJN

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Convection-enhanced delivery (CED) is a novel approach for delivering drugs directly into brain tumors by intracranial infusion, enabling the distribution of high drug concentrations over large tissue volumes. This study was designed to present a method for binding methotrexate (MTX) to unique crystalline, highly ordered and superparamagnetic maghemite nanoparticles via human serum albumin (HSA) coating, optimized for CED treatments of gliomas. Naked nanoparticles and HSA- or polyethylene glycol (PEG)-coated nanoparticles with/without MTX were studied. In vitro results showed no toxicity and a similar cell-kill efficacy of the MTX-loaded particles via HSA coating to that of free MTX, while MTX-loaded particles via PEG coating showed low efficacy. In vivo, the PEG-coated nanoparticles provided the largest distributions in normal rat brain and long clearance times, but due to their low efficacy in vitro, were not considered optimal. The naked nanoparticles provided the smallest distributions and shortest clearance times. The HSA-coated nanoparticles (with/without MTX) provided good distributions and long clearance times (nearly 50% of the distribution volume remained in the brain 3 weeks post treatment). No MTX-related toxicity was noted. These results suggest that the formulation in which HSA was bound to our nanoparticles via a unique precipitation method, and MTX was bound covalently to the HSA, could enable efficient and stable drug loading with no apparent toxicity. The cell-kill efficacy of the bound MTX remained similar to that of free MTX, and the nanoparticles presented efficient distribution volumes and slow clearance times in vivo, suggesting that these particles are optimal for CED.

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“…Figure 1 illustrates that the covalent conjugation of bFGF to the γ-Fe 2 O 3 nanoparticles is based on the presence of gelatin thin layer on the surface of these nanoparticles, as shown in Figure 2A and B and described previously. 44 The surface gelatin provides functional groups, eg, primary amines and hydroxyls, through which functionalization of these nanoparticles with activated double bonds, via the Michael addition reaction, was accomplished with excess DVS. The residual activated double bonds of the γ-Fe 2 O 3 -DVS nanoparticles were then used for covalent binding of the bFGF to the surface of the nanoparticles, again via the Michael addition reaction.…”

Section: Resultsmentioning

confidence: 99%

Novel magnetic fibrin hydrogel scaffolds containing thrombin and growth factors conjugated iron oxide nanoparticles for tissue engineering

Ziv-Polat¹,

Skaat²,

Shahar³

et al. 2012

IJN

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Novel tissue-engineered magnetic fibrin hydrogel scaffolds were prepared by the interaction of thrombin-conjugated iron oxide magnetic nanoparticles with fibrinogen. In addition, stabilization of basal fibroblast growth factor (bFGF) was achieved by the covalent and physical conjugation of the growth factor to the magnetic nanoparticles. Adult nasal olfactory mucosa (NOM) cells were seeded in the transparent fibrin scaffolds in the absence or presence of the free or conjugated bFGF-iron oxide nanoparticles. The conjugated bFGF enhanced significantly the growth and differentiation of the NOM cells in the fibrin scaffolds, compared to the same or even five times higher concentration of the free bFGF. In the presence of the bFGFconjugated magnetic nanoparticles, the cultured NOM cells proliferated and formed a threedimensional interconnected network composed mainly of tapered bipolar cells. The magnetic properties of these matrices are due to the integration of the thrombin-and bFGF-conjugated magnetic nanoparticles within the scaffolds. The magnetic properties of these scaffolds may be used in future work for various applications, such as magnetic resonance visualization of the scaffolds after implantation and reloading the scaffolds via magnetic forces with bioactive agents, eg, growth factors bound to the iron oxide magnetic nanoparticles.

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Synthesis and characterization of nano‐ and micron‐sized iron oxide and iron particles for biomedical applications

Cited by 12 publications

References 56 publications

Bioactive magnetic near Infra-Red fluorescent core-shell iron oxide/human serum albumin nanoparticles for controlled release of growth factors for augmentation of human mesenchymal stem cell growth and differentiation

Bioactive magnetic near Infra-Red fluorescent core-shell iron oxide/human serum albumin nanoparticles for controlled release of growth factors for augmentation of human mesenchymal stem cell growth and differentiation

Convection-enhanced delivery of methotrexate-loaded maghemite nanoparticles

Novel magnetic fibrin hydrogel scaffolds containing thrombin and growth factors conjugated iron oxide nanoparticles for tissue engineering

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