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. 2020 Jan 15;7(1):191139.
doi: 10.1098/rsos.191139. eCollection 2020 Jan.

The Cell Uptake Properties and Hyperthermia Performance of Zn 0.5 Fe 2.5 O 4/SiO 2 Nanoparticles as Magnetic Hyperthermia Agents

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Free PMC article

The Cell Uptake Properties and Hyperthermia Performance of Zn 0.5 Fe 2.5 O 4/SiO 2 Nanoparticles as Magnetic Hyperthermia Agents

Runsheng Wang et al. R Soc Open Sci. .
Free PMC article

Abstract

Zn0.5Fe2.5O4 nanoparticles (NPs) of 22 nm are synthesized by a one-pot approach and coated with silica for magnetic hyperthermia agents. The NPs exhibit superparamagnetic characteristics, high-specific absorption rate (SAR) (1083 wg-1, f = 430 kHz, H = 27 kAm-1), large saturation magnetization (M s = 85 emu g-1), excellent colloidal stability and low cytotoxicity. The cell uptake properties have been investigated by Prussian blue staining, transmission electron microscopy and the inductively coupled plasma-mass spectrometer, which resulted in time-dependent and concentration-dependent internalization. The internalization appeared between 0.5 and 2 h, the NPs were mainly located in the lysosomes and kept in good dispersion after incubation with human osteosarcoma MG-63 cells. Then, the relationship between cell uptake and magnetic hyperthermia performance was studied. Our results show that the hyperthermia efficiency was related to the amount of internalized NPs in the tumour cells, which was dependent on the concentration and incubation time. Interestingly, the NPs could still induce tumour cells to apoptosis/necrosis when extracellular NPs were rinsed, but the cell kill efficiency was lower than that of any rinse group, which indicated that local temperature rise was the main factor that induced tumour cells to death. Our findings suggest that this high SAR and biocompatible silica-coated Zn0.5Fe2.O4 NPs could serve as new agents for magnetic hyperthermia.

Keywords: cell uptake; endocytosis; magnetic hyperthermia; magnetite nanoparticles.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1.
Figure 1.
(a) TEM micrographs of Zn0.5Fe2.5O4 NPs. (b) High-resolution TEM image of Zn0.5Fe2.5O4 NPs. (c) TEM micrographs of silica-coated Zn0.5Fe2.5O4 NPs. (d) XRD pattern of Zn0.5Fe2.5O4/SiO2 NPs, the main reflections are (220), (311), (222), (400), (511), (440) according to PDF#86-0509-jade. (e) Hysteresis loop for 22 nm Zn0.5Fe2.5O4/SiO2 NPs recorded at room temperature pointing to the superparamagnetic characteristics of NPs. (f) Field dependence of SAR for Zn0.5Fe2.5O4/SiO2 NPs. (g) Heating curves of aqueous solutions of 22 nm Zn0.5Fe2.5O4/SiO2 NPs (1 mg NPs ml−1).
Figure 2.
Figure 2.
The cytotoxicity of Zn0.5Fe2.5O4/SiO2 NPs to MEF (a) and human osteosarcoma MG-63 (b) cells was assessed by the CCK-8 assay. Cells without NPs were used as control groups. Concentration-dependent cytotoxic effects of NPs were evaluated after 24 and 48 h incubation. Results are represented as mean ± s.e.m. Note: **significant difference from control (p < 0.01); ***significant difference from control (p < 0.005).
Figure 3.
Figure 3.
Human osteosarcoma MG-63 cells were incubated with various concentrations (a) control, (b) 6.25 µg ml−1, (c) 12.5 µg ml−1, (d) 25 µg ml−1, (e) 50 µg ml−1, (f) 100 µg ml−1, (g) 200 µg ml−1 of Zn0.5Fe2.5O4/SiO2 for 24 h. The human osteosarcoma MG-63 cells were stained blue at the concentration of 6.25 µg ml−1and the colour became thicker with the increase in NP concentrations.
Figure 4.
Figure 4.
Human osteosarcoma MG-63 cells were incubated with 20 µg ml−1 Zn0.5Fe2.5O4/SiO2 NPs for different times ((a) control, (b) 0.5 h, (c) 2 h, (d) 4 h, (e) 6 h, (f) 8 h, (g) 10 h, (h) 12 h). The cytoplasm was stained blue at 0.5 h and became thicker with incubation time.
Figure 5.
Figure 5.
TEM characterization of human osteosarcoma MG-63 cell incubation with 200 µg ml−1 Zn0.5Fe2.5O4/SiO2 NPs for 0.5 h (a,b), 2 h (c, d), 24 h (e,f). The NPs just attached to the cytomembrane did not internalize into the cytoplasm at 0.5 h incubation. However, the NPs internalized into human osteosarcoma MG-63 cells and were located in the lysosomes after 2 h incubation. With the extension of the incubation time, the amount of NPs in lysosomes gradually increased.
Figure 6.
Figure 6.
The amounts of iron per cell (in pg) determined by the elemental analysis are reported for human osteosarcoma MG-63 cell incubation with 200 µg ml−1 Zn0.5Fe2.5O4/SiO2 for different times (0.5, 2, 4, 6, 8, 10, 12 h). These values indicate the amounts of iron internalized into the tumour cells. The iron contents were estimated by ICP-MS measurements of the treated cells. All points have been acquired in triplicate.
Figure 7.
Figure 7.
(a) Apoptotic assay of human osteosarcoma MG-63 cells incubated with Zn0.5Fe2.5O4/SiO2 for different times (0.5, 2, 6, 10 h) after being exposed to AMF (f = 430 kHz, H = 11 kAm−1). Human osteosarcoma MG-63 cells without NPs or AMF were used as a control group. Human osteosarcoma MG-63 cells with NPs but without AMF were used as an another control group (NPs group). (b) The fluorescence imaging of human osteosarcoma MG-63 cells after magnetic hyperthermia treatment. (c) TEM imaging of human osteosarcoma MG-63 cells incubated with Zn0.5Fe2.5O4/SiO2 for 2 h after magnetic hyperthermia.

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