Using thermal energy produced by irradiation of Mn–Zn ferrite magnetic nanoparticles (MZF-NPs) for heat-inducible gene expression

Tang, Qiusha; Zhang, Dongsheng; Cong, Xiaoming; Wan, Meiling; Jin, Liqiang

doi:10.1016/j.biomaterials.2008.01.038

“…The procedure used by Tang et al 7 was followed, according to which Fe 3 O 4 nanoparticles are dispersed in 150 mM NaCl and diluted to various concentrations (0.5, 1.0, 1.5, 2.0, and 2.5 mg/mL). A 5 mL sample of fluid was placed in a 60 mm diameter dish and then exposed to a high-frequency alternating electromagnetic field (SPG-06A).…”

Section: In Vitro Heating Of Fe 3 Omentioning

confidence: 99%

Biocompatibility of magnetic Fe3O4 nanoparticles and their cytotoxic effect on MCF-7 cells

Chen

¹

,

Tang²,

Li³

et al. 2012

IJN

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Background:The objective of this study was to evaluate the synthesis and biocompatibility of Fe 3 O 4 nanoparticles and investigate their therapeutic effects when combined with magnetic fluid hyperthermia on cultured MCF-7 cancer cells. Methods: Magnetic Fe 3 O 4 nanoparticles were prepared using a coprecipitation method. The appearance, structure, phase composition, functional groups, surface charge, magnetic susceptibility, and release in vitro were characterized by transmission electron microscopy, x-ray diffraction, scanning electron microscopy-energy dispersive x-ray spectroscopy, and a vibrating sample magnetometer. Blood toxicity, in vitro toxicity, and genotoxicity were investigated. Therapeutic effects were evaluated by MTT [3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide] and flow cytometry assays. Results: Transmission electron microscopy revealed that the shapes of the Fe 3 O 4 nanoparticles were approximately spherical, with diameters of about 26.1 ± 5.2 nm. Only the spinel phase was indicated in a comparison of the x-ray diffraction data with Joint Corporation of Powder Diffraction Standards (JCPDS) X-ray powder diffraction files. The O-to-Fe ratio of the Fe 3 O 4 was determined by scanning electron microscopy-energy dispersive x-ray spectroscopy elemental analysis, and approximated pure Fe 3 O 4 . The vibrating sample magnetometer hysteresis loop suggested that the Fe 3 O 4 nanoparticles were superparamagnetic at room temperature. MTT experiments showed that the toxicity of the material in mouse fibroblast (L-929) cell lines was between Grade 0 to Grade 1, and that the material lacked hemolysis activity. The acute toxicity (LD 50 ) was 8.39 g/kg. Micronucleus testing showed no genotoxic effects. Pathomorphology and blood biochemistry testing demonstrated that the Fe 3 O 4 nanoparticles had no effect on the main organs and blood biochemistry in a rabbit model. MTT and flow cytometry assays revealed that Fe 3 O 4 nano magnetofluid thermotherapy inhibited MCF-7 cell proliferation, and its inhibitory effect was dose-dependent according to the Fe 3 O 4 nano magnetofluid concentration. Conclusion: The Fe 3 O 4 nanoparticles prepared in this study have good biocompatibility and are suitable for further application in tumor hyperthermia.

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“…The complexes were then incubated at room temperature for 30 minutes. As a reference, 10 PEI (complexed with DNA at an N/P ratio of 7) or commercially-available transfection reagents, such as Lipofectamine™ (Invitrogen, Carlsbad, CA) were used in accordance with the manufacturer's instructions.…”

Section: Cell Transfectionmentioning

confidence: 99%

A study on the preparation and characterization of plasmid DNA and drug-containing magnetic nanoliposomes for the treatment of tumors

Wang¹,

Wang²,

Zhang³

et al. 2011

IJN

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Purpose: To explore the preparation and characterization of a novel nanosized magnetic liposome containing the PEI-As 2 O 3 /Mn 0.5 Zn 0.5 Fe 2 O 4 complex. Methods: Mn 0.5 Zn 0.5 Fe 2 O 4 and As 2 O 3 /Mn 0.5 Zn 0.5 Fe 2 O 4 nanoparticles were prepared by chemical coprecipitation and loaded with PEI. The PEI- As 2 O 3 /Mn 0.5 Zn 0.5 Fe 2 O 4 complex was characterized using transmission electron and scanning electron microscopy, X-ray diffraction, energy dispersive spectrometry, and Fourier transform infrared spectroscopy. Cell transfection experiments were performed to evaluate the transfect efficiency. Magnetic nanoliposomes were prepared by rotatory evaporation and their shape, diameter, and thermodynamic characteristics were observed. Results: Mn 0.5 Zn 0.5 Fe 2 O 4 and PEI-As 2 O 3 /Mn 0.5 Zn 0.5 Fe 2 O 4 nanoparticles were spherical, with an average diameter of 20–40 nm. PEI-As 2 O 3 /Mn 0.5 Zn 0.5 Fe 2 O 4 was an appropriate carrier for the delivery of a foreign gene to HepG2 cells. Energy dispersive spectrometry results confirmed the presence of the elements nitrogen and arsenic. Nanoliposomes of approximately 100 nm were observed under a transmission electron microscope. Upon exposure to an alternating magnetic field, they also had good magnetic responsiveness, even though Mn 0.5 Zn 0.5 Fe 2 O 4 was modified by PEI and encased in liposomes. Temperatures increased to 37°C–54°C depending on different concentrations of PEI-As 2 O 3 /Mn 0.5 Zn 0.5 Fe 2 O 4 and remained stable thereafter. Conclusion: Our results suggest that PEI-As 2 O 3 /Mn 0.5 Zn ...

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“…[16][17][18] In previous research, 19,20 we developed a novel heat-inducible gene expression system in which thermal energy generated by Mn-Zn ferrite magnetic nanoparticles (MZF-NPs) under an alternating magnetic field was used to activate gene expression. There were four main advantages to this system: 1) utilization of the relatively low Curie point of MZF-NPs to control the in vivo hyperthermia temperature and therefore achieving safe and effective heat-inducible transgene expression; 21,22 2) use of the promoter of HSPs that are conserved among species from bacteria to humans.…”

Section: Introductionmentioning

confidence: 99%

Combination of PEI-Mn0.5Zn0.5Fe2O4 nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma

Tang

¹

,

Lu

²

,

Chen

³

et al. 2015

IJN

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Background To explore a new combination of thermal treatment and gene therapy for hepatoma, a heat-inducible herpes simplex virus thymidine kinase /ganciclovir ( HSV - TK /GCV) gene therapy system was developed in which thermal energy generated by Mn 0.5 Zn 0.5 Fe 2 O 4 nanoparticles (MZF-NPs) under an alternating magnetic field was used to activate gene expression. Methods First, a recombinant eukaryotic plasmid, pHsp 70- HSV-TK , was constructed as a target gene for therapy. This recombinant plasmid was used to transfect SMMC-7721 hepatoma cells and the gene expression was evaluated. Magnet-induced heating was then applied to cells to assess the antihepatoma effects of the polyethylenimine (PEI)-MZF-NPs/pHsp 70- HSV-TK /GCV complex, in vitro and in vivo. Results The results showed that cells were successfully transfected with pHsp 70- HSV-TK and that expression levels of HSV-TK remained stable. Both in vitro and in vivo results indicated that the combination of gene therapy and heat treatment resulted in better therapeutic effects than heating-alone group. The rates of apoptosis and necrosis in the combined treatment group were 49.0% and 7.21%, respectively. The rate of inhibition of cell proliferation in the combined treatment group was significantly higher (87.5%) than that in the heating-alone group (65.8%; P <0.01). The tumor volume and mass inhibition rates of the combined treatment group were 91.3% and 87.91%, respectively, and were significantly higher than the corresponding rates of the heating-alone group (70.41% and 57.14%; P <0.01). The expression levels of Stat3 and Bcl-xL messenger RNA and p-Stat3 and Bcl-xL protein in the combined treatment group were significantly lower than those in the other groups ( P <0.01). The expression levels of Bax messenger RNA and protein in the recombinant plasmid group were significantly higher than those in the other groups ( P <0.01). Conclusion It can therefore be concluded that the combined application of heat treatment and gene therapy has a synergistic and complementary effect and that PEI-MZF-NPs can simultaneously act both as a nonviral gene vector and a magnet-induced source of heat, thereby representing a viable approach for the treatment of cancer.

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Using thermal energy produced by irradiation of Mn–Zn ferrite magnetic nanoparticles (MZF-NPs) for heat-inducible gene expression

Cited by 66 publications

References 23 publications

Biocompatibility of magnetic Fe3O4 nanoparticles and their cytotoxic effect on MCF-7 cells

Biocompatibility of magnetic Fe3O4 nanoparticles and their cytotoxic effect on MCF-7 cells

A study on the preparation and characterization of plasmid DNA and drug-containing magnetic nanoliposomes for the treatment of tumors

Combination of PEI-Mn0.5Zn0.5Fe2O4 nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma

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