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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.


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Peroxidase-like activity assays of M-HFn nanoparticles.Notes: M-HFn nanoparticles with different sizes of core catalyzed the oxidation of peroxidase substrates in the presence of H2O2. (A) TMB as the substrate to give a deep blue color product. (B) DAB as the substrate to give a deep brown color product. Color intensity changes with (a) HFn cage, (b) M-HFn1000, (c) M-HFn3000, (d) M-HFn5000, and (e) M-HFn7000. (C) The peroxidase-like activity of M-HFn nanoparticle is size dependent; larger M-HFn nanoparticles show higher peroxidase-like activity (TMB as the substrate).Abbreviations: HFn, H chain ferritin; M-HFn, ferrimagnetic H-ferritin; TMB, 3,3′,5,5′-tetramethylbenzidine; DAB, 3,3′-diaminobenzidine tetrahydrochloride.
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f4-ijn-10-2619: Peroxidase-like activity assays of M-HFn nanoparticles.Notes: M-HFn nanoparticles with different sizes of core catalyzed the oxidation of peroxidase substrates in the presence of H2O2. (A) TMB as the substrate to give a deep blue color product. (B) DAB as the substrate to give a deep brown color product. Color intensity changes with (a) HFn cage, (b) M-HFn1000, (c) M-HFn3000, (d) M-HFn5000, and (e) M-HFn7000. (C) The peroxidase-like activity of M-HFn nanoparticle is size dependent; larger M-HFn nanoparticles show higher peroxidase-like activity (TMB as the substrate).Abbreviations: HFn, H chain ferritin; M-HFn, ferrimagnetic H-ferritin; TMB, 3,3′,5,5′-tetramethylbenzidine; DAB, 3,3′-diaminobenzidine tetrahydrochloride.

Mentions: Peroxidase-like activity of M-HFn nanoparticles tested at constant concentration of HFn nicely increased with size of M-HFn cores (Figure 4). M-HFn nanoparticles catalyze the oxidation of peroxidase substrates TMB and DAB in the presence of H2O2 to give a blue color (Figure 4A) and a brown color product (Figure 4B), respectively. It is clear that the M-HFn nanoparticles with larger size of cores have higher peroxidase-like activity and absorbance. The M-HFn7000 nanoparticles have nearly five times absorbance compared to M-HFn1000 at 10 minutes (Figure 4C).


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)

Peroxidase-like activity assays of M-HFn nanoparticles.Notes: M-HFn nanoparticles with different sizes of core catalyzed the oxidation of peroxidase substrates in the presence of H2O2. (A) TMB as the substrate to give a deep blue color product. (B) DAB as the substrate to give a deep brown color product. Color intensity changes with (a) HFn cage, (b) M-HFn1000, (c) M-HFn3000, (d) M-HFn5000, and (e) M-HFn7000. (C) The peroxidase-like activity of M-HFn nanoparticle is size dependent; larger M-HFn nanoparticles show higher peroxidase-like activity (TMB as the substrate).Abbreviations: HFn, H chain ferritin; M-HFn, ferrimagnetic H-ferritin; TMB, 3,3′,5,5′-tetramethylbenzidine; DAB, 3,3′-diaminobenzidine tetrahydrochloride.
© Copyright Policy
Related In: Results  -  Collection

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

f4-ijn-10-2619: Peroxidase-like activity assays of M-HFn nanoparticles.Notes: M-HFn nanoparticles with different sizes of core catalyzed the oxidation of peroxidase substrates in the presence of H2O2. (A) TMB as the substrate to give a deep blue color product. (B) DAB as the substrate to give a deep brown color product. Color intensity changes with (a) HFn cage, (b) M-HFn1000, (c) M-HFn3000, (d) M-HFn5000, and (e) M-HFn7000. (C) The peroxidase-like activity of M-HFn nanoparticle is size dependent; larger M-HFn nanoparticles show higher peroxidase-like activity (TMB as the substrate).Abbreviations: HFn, H chain ferritin; M-HFn, ferrimagnetic H-ferritin; TMB, 3,3′,5,5′-tetramethylbenzidine; DAB, 3,3′-diaminobenzidine tetrahydrochloride.
Mentions: Peroxidase-like activity of M-HFn nanoparticles tested at constant concentration of HFn nicely increased with size of M-HFn cores (Figure 4). M-HFn nanoparticles catalyze the oxidation of peroxidase substrates TMB and DAB in the presence of H2O2 to give a blue color (Figure 4A) and a brown color product (Figure 4B), respectively. It is clear that the M-HFn nanoparticles with larger size of cores have higher peroxidase-like activity and absorbance. The M-HFn7000 nanoparticles have nearly five times absorbance compared to M-HFn1000 at 10 minutes (Figure 4C).

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