Enhanced cellular uptake of aminosilane-coated superparamagnetic iron oxide nanoparticles in mammalian cell lines

Xiao-Ming Zhu¹, Yi-Xiang J Wang¹, Ken Cham-Fai Leung^2,3, Siu-Fung Lee², Feng Zhao¹, Da-Wei Wang2, Josie MY Lai⁴, Chao Wan⁴, Christopher HK Cheng⁴, Anil T Ahuja^1
1Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR; ²Institute of Molecular Functional Materials and Department of Chemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR; ³Institute of Creativity and Department of Chemistry, The Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong SAR; ⁴School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong

Purpose: To compare the cellular uptake efficiency and cytotoxicity of aminosilane (SiO₂-NH₂)-coated superparamagnetic iron oxide (SPIO@SiO₂-NH₂) nanoparticles with three other types of SPIO nanoparticles coated with SiO₂ (SPIO@SiO₂), dextran (SPIO@dextran), or bare SPIO in mammalian cell lines.
Materials and methods: Four types of monodispersed SPIO nanoparticles with a SPIO core size of 7 nm and an overall size in a range of 7–15 nm were synthesized. The mammalian cell lines of MCF-7, MDA-MB-231, HT-29, RAW264.7, L929, HepG2, PC-3, U-87 MG, and mouse mesenchymal stem cells (MSCs) were incubated with four types of SPIO nanoparticles for 24 hours in the serum-free culture medium Dulbecco’s modified Eagle’s medium (DMEM) with 4.5 µg/mL iron concentration. The cellular uptake efficiencies of SPIO nanoparticles were compared by Prussian blue staining and intracellular iron quantification. In vitro magnetic resonance imaging of MSC pellets after SPIO labeling was performed at 3 T. The effect of each SPIO nanoparticle on the cell viability of RAW 264.7 (mouse monocyte/macrophage) cells was also evaluated.
Results: Transmission electron microscopy demonstrated surface coating with SiO₂-NH₂, SiO₂, and dextran prevented SPIO nanoparticle aggregation in DMEM culture medium. MCF-7, MDA-MB-231, and HT-29 cells failed to show notable iron uptake. For all the remaining six cell lines, Prussian blue staining and intracellular iron quantification demonstrated that SPIO@SiO₂-NH₂ nanoparticles had the highest cellular uptake efficiency. SPIO@SiO₂-NH₂, bare SPIO, and SPIO@dextran nanoparticles did not affect RAW 264.7 cell viability up to 200 µg Fe/mL, while SPIO@SiO₂ reduced RAW 264.7 cell viability from 10 to 200 µg Fe/mL in a dose-dependent manner.
Conclusion: Cellular uptake efficiency of SPIO nanoparticles depends on both the cell type and SPIO surface characteristics. Aminosilane surface coating enhanced the cellular uptake efficiency without inducing cytotoxicity in a number of cell lines.

Keywords: magnetic nanoparticles, SPIO, iron oxide, surface coating, cellular uptake

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