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Enhanced magnetic resonance imaging and staining of cancer cells using ferrimagnetic H-ferritin nanoparticles with increasing core size.

Cai Y, Cao C, He X, Yang C, Tian L, Zhu R, Pan Y - Int J Nanomedicine (2015)

Bottom Line: 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.The saturation magnetization (M(s)), relaxivity, and peroxidase-like activity of synthesized M-HFn nanoparticles were monotonously increased with the size of ferrimagnetic cores.

View Article: PubMed Central - PubMed

Affiliation: France-China Bio-Mineralization and Nano-Structures Laboratory, Key Laboratory of the Earth and Planetary Physics, Institute of Geology and Geophysics, Chinese Academy of Sciences, People's Republic of China ; Paleomagnetism and Geochronology Laboratory, Key Laboratory of the Earth and Planetary Physics, Institute of Geology and Geophysics, Chinese Academy of Sciences, People's Republic of China ; University of Chinese Academy of Sciences, Beijing, People's Republic of China.

ABSTRACT

Purpose: 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.

Materials and methods: 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.

Results: 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 r2 of 321 mM(-1) s(-1), allowing to detect MDA-MB-231 breast cancer cells as low as 10(4) cells mL(-1).

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Native PAGE analysis of assembled HFn cage structure of M-HFn nanoparticles.Notes: Gel was stained with (A) potassium ferrocyanide and (B) Coomassie Brilliant Blue R250. Lane 1, HFn cage; lane 2, M-HFn1000; lane 3, M-HFn3000; lane 4, M-HFn5000; and lane 5, M-HFn7000. (C) CD spectra determination of the secondary protein structural stability of M-HFn nanoparticles.Abbreviations: HFn, H chain ferritin; M-HFn, ferrimagnetic H-ferritin; PAGE, polyacrylamide gel electrophoresis; CD, circular dichroism; PBS, phosphate-buffered saline.
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f2-ijn-10-2619: Native PAGE analysis of assembled HFn cage structure of M-HFn nanoparticles.Notes: Gel was stained with (A) potassium ferrocyanide and (B) Coomassie Brilliant Blue R250. Lane 1, HFn cage; lane 2, M-HFn1000; lane 3, M-HFn3000; lane 4, M-HFn5000; and lane 5, M-HFn7000. (C) CD spectra determination of the secondary protein structural stability of M-HFn nanoparticles.Abbreviations: HFn, H chain ferritin; M-HFn, ferrimagnetic H-ferritin; PAGE, polyacrylamide gel electrophoresis; CD, circular dichroism; PBS, phosphate-buffered saline.

Mentions: Native PAGE and CD spectra of the synthesized M-HFn nanoparticles show that the synthesized M-HFn nanoparticles have intact protein cages (Figure 2). The gradual darkening of blue color from lane 2 to lane 5 (Figure 2A) indicates the increase in iron contents in M-HFn1000, M-HFn3000, M-HFn5000, and M-HFn7000. Comparable protein-staining bands from lane 2 to lane 5 with native HFn protein cage in lane 1 (Figure 2B) and the CD spectra (Figure 2C) indicate that the protein structure of HFn cages/shells in the synthesized M-HFn nanoparticles is likely intact after the mineralization process.


Enhanced magnetic resonance imaging and staining of cancer cells using ferrimagnetic H-ferritin nanoparticles with increasing core size.

Cai Y, Cao C, He X, Yang C, Tian L, Zhu R, Pan Y - Int J Nanomedicine (2015)

Native PAGE analysis of assembled HFn cage structure of M-HFn nanoparticles.Notes: Gel was stained with (A) potassium ferrocyanide and (B) Coomassie Brilliant Blue R250. Lane 1, HFn cage; lane 2, M-HFn1000; lane 3, M-HFn3000; lane 4, M-HFn5000; and lane 5, M-HFn7000. (C) CD spectra determination of the secondary protein structural stability of M-HFn nanoparticles.Abbreviations: HFn, H chain ferritin; M-HFn, ferrimagnetic H-ferritin; PAGE, polyacrylamide gel electrophoresis; CD, circular dichroism; PBS, phosphate-buffered saline.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4388082&req=5

f2-ijn-10-2619: Native PAGE analysis of assembled HFn cage structure of M-HFn nanoparticles.Notes: Gel was stained with (A) potassium ferrocyanide and (B) Coomassie Brilliant Blue R250. Lane 1, HFn cage; lane 2, M-HFn1000; lane 3, M-HFn3000; lane 4, M-HFn5000; and lane 5, M-HFn7000. (C) CD spectra determination of the secondary protein structural stability of M-HFn nanoparticles.Abbreviations: HFn, H chain ferritin; M-HFn, ferrimagnetic H-ferritin; PAGE, polyacrylamide gel electrophoresis; CD, circular dichroism; PBS, phosphate-buffered saline.
Mentions: Native PAGE and CD spectra of the synthesized M-HFn nanoparticles show that the synthesized M-HFn nanoparticles have intact protein cages (Figure 2). The gradual darkening of blue color from lane 2 to lane 5 (Figure 2A) indicates the increase in iron contents in M-HFn1000, M-HFn3000, M-HFn5000, and M-HFn7000. Comparable protein-staining bands from lane 2 to lane 5 with native HFn protein cage in lane 1 (Figure 2B) and the CD spectra (Figure 2C) indicate that the protein structure of HFn cages/shells in the synthesized M-HFn nanoparticles is likely intact after the mineralization process.

Bottom Line: 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.The saturation magnetization (M(s)), relaxivity, and peroxidase-like activity of synthesized M-HFn nanoparticles were monotonously increased with the size of ferrimagnetic cores.

View Article: PubMed Central - PubMed

Affiliation: France-China Bio-Mineralization and Nano-Structures Laboratory, Key Laboratory of the Earth and Planetary Physics, Institute of Geology and Geophysics, Chinese Academy of Sciences, People's Republic of China ; Paleomagnetism and Geochronology Laboratory, Key Laboratory of the Earth and Planetary Physics, Institute of Geology and Geophysics, Chinese Academy of Sciences, People's Republic of China ; University of Chinese Academy of Sciences, Beijing, People's Republic of China.

ABSTRACT

Purpose: 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.

Materials and methods: 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.

Results: 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 r2 of 321 mM(-1) s(-1), allowing to detect MDA-MB-231 breast cancer cells as low as 10(4) cells mL(-1).

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus