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Polyetherimide-grafted Fe₃O₄@SiO2₂ nanoparticles as theranostic agents for simultaneous VEGF siRNA delivery and magnetic resonance cell imaging.

Li T, Shen X, Chen Y, Zhang C, Yan J, Yang H, Wu C, Zeng H, Liu Y - Int J Nanomedicine (2015)

Bottom Line: Low cytotoxicity and hemolyticity against human red blood cells showed the excellent biocompatibility of the multifunctional nanocomposites, and also no significant coagulation was observed.The nanocomposites maintain their superparamagnetic property at room temperature and no appreciable change in magnetism, even after PEI modification.Our data highlight multifunctional Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites as a potential platform for simultaneous gene delivery and MR cell imaging, which are promising as theranostic agents for cancer treatment and diagnosis in the future.

View Article: PubMed Central - PubMed

Affiliation: Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, People's Republic of China.

ABSTRACT
Engineering a safe and high-efficiency delivery system for efficient RNA interference is critical for successful gene therapy. In this study, we designed a novel nanocarrier system of polyethyleneimine (PEI)-modified Fe3O4@SiO2, which allows high efficient loading of VEGF small hairpin (sh)RNA to form Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites for VEGF gene silencing as well as magnetic resonance (MR) imaging. The size, morphology, particle stability, magnetic properties, and gene-binding capacity and protection were determined. Low cytotoxicity and hemolyticity against human red blood cells showed the excellent biocompatibility of the multifunctional nanocomposites, and also no significant coagulation was observed. The nanocomposites maintain their superparamagnetic property at room temperature and no appreciable change in magnetism, even after PEI modification. The qualitative and quantitative analysis of cellular internalization into MCF-7 human breast cancer cells by Prussian blue staining and inductively coupled plasma atomic emission spectroscopy analysis, respectively, demonstrated that the Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites could be easily internalized by MCF-7 cells, and they exhibited significant inhibition of VEGF gene expression. Furthermore, the MR cellular images showed that the superparamagnetic iron oxide core of our Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites could also act as a T2-weighted contrast agent for cancer MR imaging. Our data highlight multifunctional Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites as a potential platform for simultaneous gene delivery and MR cell imaging, which are promising as theranostic agents for cancer treatment and diagnosis in the future.

No MeSH data available.


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STEM and HAADF-STEM-EDS mapping images of Fe3O4@SiO2 nanoparticles O, Si, and Fe.Notes: (A) STEM of Fe3O4@SiO2 nanoparticles (inset: higher-magnification image of STEM). (B–D) HAADF-STEM-EDS mapping images of Fe3O4@SiO2 revealing the O, Si, and Fe.Abbreviations: STEM, scanning transmission electron microscope; HAADF-STEM-EDS, high-angle annular dark field scanning transmission electron microscopy–energy-dispersive X-ray spectrometry; O, oxygen; Si, silica; Fe, iron.
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f3-ijn-10-4279: STEM and HAADF-STEM-EDS mapping images of Fe3O4@SiO2 nanoparticles O, Si, and Fe.Notes: (A) STEM of Fe3O4@SiO2 nanoparticles (inset: higher-magnification image of STEM). (B–D) HAADF-STEM-EDS mapping images of Fe3O4@SiO2 revealing the O, Si, and Fe.Abbreviations: STEM, scanning transmission electron microscope; HAADF-STEM-EDS, high-angle annular dark field scanning transmission electron microscopy–energy-dispersive X-ray spectrometry; O, oxygen; Si, silica; Fe, iron.

Mentions: The multistep processes for fabrication of Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites are shown in Figure 1, which is similar to previously reported processes with minor modifications.9 The Fe3O4 nanoparticles were coated with a silica shell to form core/shell structural Fe3O4@SiO2 nanoparticles.31,32 PEI was coated on the Fe3O4@SiO2 nanoparticle surfaces by electrostatic interaction to enhance targeted gene adsorption and transfection efficiency. Transmission electron microscopy (TEM) and STEM were used to characterize the structure and morphology of Fe3O4@SiO2 nanoparticles and Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites. The TEM images confirmed that both Fe3O4@SiO2 nanoparticles (Figure 2A) and Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites (Figure 2B) were uniform, spherical, and well dispersed in suspension (Figure 2C and 2D). A clear core/shell structure was observed for Fe3O4@SiO2 nanoparticles with a mean diameter of 57 nm. Of interest, the mean diameter and average shell thickness of Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites did not change in an obvious manner, even after PEI modification and VEGF shRNA absorption. This suggests that PEI modification and VEGF shRNA complexation did not affect the morphology and size distribution of the nanoparticles. This core/shell structure was also clearly confirmed by the STEM image of Fe3O4@SiO2 nanoparticles (Figure 3A). Compositional analysis of the nanocomposite was carried out using energy-dispersive X-ray spectroscopy mapping (Figure 3B–D); the signals for the oxygen, silica, and iron elements were clearly detected in the nanoparticles. All of the aforementioned data demonstrated that core/shell structural Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites could be successfully obtained by our modified method.


Polyetherimide-grafted Fe₃O₄@SiO2₂ nanoparticles as theranostic agents for simultaneous VEGF siRNA delivery and magnetic resonance cell imaging.

Li T, Shen X, Chen Y, Zhang C, Yan J, Yang H, Wu C, Zeng H, Liu Y - Int J Nanomedicine (2015)

STEM and HAADF-STEM-EDS mapping images of Fe3O4@SiO2 nanoparticles O, Si, and Fe.Notes: (A) STEM of Fe3O4@SiO2 nanoparticles (inset: higher-magnification image of STEM). (B–D) HAADF-STEM-EDS mapping images of Fe3O4@SiO2 revealing the O, Si, and Fe.Abbreviations: STEM, scanning transmission electron microscope; HAADF-STEM-EDS, high-angle annular dark field scanning transmission electron microscopy–energy-dispersive X-ray spectrometry; O, oxygen; Si, silica; Fe, iron.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495783&req=5

f3-ijn-10-4279: STEM and HAADF-STEM-EDS mapping images of Fe3O4@SiO2 nanoparticles O, Si, and Fe.Notes: (A) STEM of Fe3O4@SiO2 nanoparticles (inset: higher-magnification image of STEM). (B–D) HAADF-STEM-EDS mapping images of Fe3O4@SiO2 revealing the O, Si, and Fe.Abbreviations: STEM, scanning transmission electron microscope; HAADF-STEM-EDS, high-angle annular dark field scanning transmission electron microscopy–energy-dispersive X-ray spectrometry; O, oxygen; Si, silica; Fe, iron.
Mentions: The multistep processes for fabrication of Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites are shown in Figure 1, which is similar to previously reported processes with minor modifications.9 The Fe3O4 nanoparticles were coated with a silica shell to form core/shell structural Fe3O4@SiO2 nanoparticles.31,32 PEI was coated on the Fe3O4@SiO2 nanoparticle surfaces by electrostatic interaction to enhance targeted gene adsorption and transfection efficiency. Transmission electron microscopy (TEM) and STEM were used to characterize the structure and morphology of Fe3O4@SiO2 nanoparticles and Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites. The TEM images confirmed that both Fe3O4@SiO2 nanoparticles (Figure 2A) and Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites (Figure 2B) were uniform, spherical, and well dispersed in suspension (Figure 2C and 2D). A clear core/shell structure was observed for Fe3O4@SiO2 nanoparticles with a mean diameter of 57 nm. Of interest, the mean diameter and average shell thickness of Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites did not change in an obvious manner, even after PEI modification and VEGF shRNA absorption. This suggests that PEI modification and VEGF shRNA complexation did not affect the morphology and size distribution of the nanoparticles. This core/shell structure was also clearly confirmed by the STEM image of Fe3O4@SiO2 nanoparticles (Figure 3A). Compositional analysis of the nanocomposite was carried out using energy-dispersive X-ray spectroscopy mapping (Figure 3B–D); the signals for the oxygen, silica, and iron elements were clearly detected in the nanoparticles. All of the aforementioned data demonstrated that core/shell structural Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites could be successfully obtained by our modified method.

Bottom Line: Low cytotoxicity and hemolyticity against human red blood cells showed the excellent biocompatibility of the multifunctional nanocomposites, and also no significant coagulation was observed.The nanocomposites maintain their superparamagnetic property at room temperature and no appreciable change in magnetism, even after PEI modification.Our data highlight multifunctional Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites as a potential platform for simultaneous gene delivery and MR cell imaging, which are promising as theranostic agents for cancer treatment and diagnosis in the future.

View Article: PubMed Central - PubMed

Affiliation: Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, People's Republic of China.

ABSTRACT
Engineering a safe and high-efficiency delivery system for efficient RNA interference is critical for successful gene therapy. In this study, we designed a novel nanocarrier system of polyethyleneimine (PEI)-modified Fe3O4@SiO2, which allows high efficient loading of VEGF small hairpin (sh)RNA to form Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites for VEGF gene silencing as well as magnetic resonance (MR) imaging. The size, morphology, particle stability, magnetic properties, and gene-binding capacity and protection were determined. Low cytotoxicity and hemolyticity against human red blood cells showed the excellent biocompatibility of the multifunctional nanocomposites, and also no significant coagulation was observed. The nanocomposites maintain their superparamagnetic property at room temperature and no appreciable change in magnetism, even after PEI modification. The qualitative and quantitative analysis of cellular internalization into MCF-7 human breast cancer cells by Prussian blue staining and inductively coupled plasma atomic emission spectroscopy analysis, respectively, demonstrated that the Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites could be easily internalized by MCF-7 cells, and they exhibited significant inhibition of VEGF gene expression. Furthermore, the MR cellular images showed that the superparamagnetic iron oxide core of our Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites could also act as a T2-weighted contrast agent for cancer MR imaging. Our data highlight multifunctional Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites as a potential platform for simultaneous gene delivery and MR cell imaging, which are promising as theranostic agents for cancer treatment and diagnosis in the future.

No MeSH data available.


Related in: MedlinePlus