A human ferritin iron oxide nano-composite magnetic resonance contrast agent
ABSTRACT Macrophages play important roles in the immunological defense system, but at the same time they are involved in inflammatory diseases such as atherosclerosis. Therefore, imaging macrophages is critical to assessing the status of these diseases. Toward this goal, a recombinant human H chain ferritin (rHFn)-iron oxide nano composite has been investigated as an MRI contrast agent for labeling macrophages. Iron oxide nanoparticles in the form of magnetite (or maghemite) with narrow size distribution were synthesized in the interior cavity of rHFn. The composite material exhibited the R(2) relaxivity comparable to known iron oxide MRI contrast agents. Furthermore, the mineralized protein cages are readily taken up by macrophages in vitro and provide significant T2* signal loss of the labeled cells. These results encourage further investigation into the development of the rHFn-iron oxide contrast agent to assess inflammatory disease status such as macrophage-rich atherosclerotic plaques in vivo.
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ABSTRACT: This study is to demonstrate the nanoscale size effect of ferrimagnetic H-ferritin (M-HFn) nanoparticles on magnetic properties, relaxivity, enzyme mimetic activities, and application in magnetic resonance imaging (MRI) and immunohistochemical staining of cancer cells. M-HFn nanoparticles with different sizes of magnetite cores in the range of 2.7-5.3 nm were synthesized through loading different amounts of iron into recombinant human H chain ferritin (HFn) shells. Core size, crystallinity, and magnetic properties of those M-HFn nanoparticles were analyzed by transmission electron microscope and low-temperature magnetic measurements. The MDA-MB-231 cancer cells were incubated with synthesized M-HFn nanoparticles for 24 hours in Dulbecco's Modified Eagle's Medium. In vitro MRI of cell pellets after M-HFn labeling was performed at 7 T. Iron uptake of cells was analyzed by Prussian blue staining and inductively coupled plasma mass spectrometry. Immunohistochemical staining by using the peroxidase-like activity of M-HFn nanoparticles was carried out on MDA-MB-231 tumor tissue paraffin sections. The saturation magnetization (M s), relaxivity, and peroxidase-like activity of synthesized M-HFn nanoparticles were monotonously increased with the size of ferrimagnetic cores. The M-HFn nanoparticles with the largest core size of 5.3 nm exhibit the strongest saturation magnetization, the highest peroxidase activity in immunohistochemical staining, and the highest r 2 of 321 mM(-1) s(-1), allowing to detect MDA-MB-231 breast cancer cells as low as 10(4) cells mL(-1). The magnetic properties, relaxivity, and peroxidase-like activity of M-HFn nanoparticles are size dependent, which indicates that M-HFn nanoparticles with larger magnetite core can significantly enhance performance in MRI and staining of cancer cells.International Journal of Nanomedicine 01/2015; 10:2619-34. DOI:10.2147/IJN.S80025 · 4.20 Impact Factor
- Chemical Reviews 02/2015; DOI:10.1021/cr400011b · 45.66 Impact Factor
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ABSTRACT: Magnetic nanomaterials find increasing application as separation agents to rapidly isolate target compounds from complex biological media (i.e., blood purification). The responsiveness of the used materials to external magnetic fields (i.e., their saturation magnetization) is one of the most critical parameters for a fast and thorough separation. In the present study, magnetite (Fe3O4) and non-oxidic cementite (Fe3C) based carbon-coated nanomagnets are characterized in detail and compared regarding their separation behavior from human whole blood. A quantification approach for iron-based nanomaterials in biological samples with strong matrix effects (here, salts in blood) based on platinum spiking is shown. Both materials are functionalized with polyethyleneglycol (PEG) to improve cytocompatibility (confirmed by cell toxicity tests) and dispersability. The separation performance is tested in two setups, namely under stationary and different flow-conditions using fresh human blood. The results reveal a superior separation behavior of the cementite based nanomagnets and strongly suggest the use of nanomaterials with high saturation magnetizations for magnetic retention under common blood flow conditions such as in veins.Advanced Functional Materials 10/2013; 23(39):4888. DOI:10.1002/adfm.201300696 · 10.44 Impact Factor