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

Abstract

Yao Cai,1–3 Changqian Cao,1,2 Xiaoqing He,1 Caiyun Yang,1–3 Lanxiang Tian,1,2 Rixiang Zhu,2 Yongxin Pan1,21France–China Bio-Mineralization and Nano-Structures Laboratory, 2Paleomagnetism and Geochronology Laboratory, Key Laboratory of the Earth and Planetary Physics, Institute of Geology and Geophysics, Chinese Academy of Sciences, 3University of Chinese Academy of Sciences, Beijing, People’s Republic of ChinaPurpose: 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 (Ms), 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 104 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.Keywords: magnetic nanoparticles, magnetoferritin, peroxidase-like activity, magnetic resonance imaging, cancer cells