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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.

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Agarose gel electrophoresis retardation assays.Notes: (A) Fe3O4@SiO2:VEGF shRNA and (C) Fe3O4@SiO2/PEI:VEGF shRNA at different weight ratios (5:1, 10:1, 20:1, 30:1, and 40:1) in water; and (B) Fe3O4@SiO2:VEGF shRNA and (D) Fe3O4@SiO2/PEI:VEGF shRNA at different weight ratios (5:1, 10:1, 20:1, 30:1, and 40:1) in 0.9% NaCl.Abbreviations: shRNA, small hairpin RNA; PEI, polyethylenimine.
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f8-ijn-10-4279: Agarose gel electrophoresis retardation assays.Notes: (A) Fe3O4@SiO2:VEGF shRNA and (C) Fe3O4@SiO2/PEI:VEGF shRNA at different weight ratios (5:1, 10:1, 20:1, 30:1, and 40:1) in water; and (B) Fe3O4@SiO2:VEGF shRNA and (D) Fe3O4@SiO2/PEI:VEGF shRNA at different weight ratios (5:1, 10:1, 20:1, 30:1, and 40:1) in 0.9% NaCl.Abbreviations: shRNA, small hairpin RNA; PEI, polyethylenimine.

Mentions: The nuclear acid-binding capability of the nanoparticles is a very important factor to consider when choosing a gene delivery carrier.41,42 The binding capacity to VEGF shRNA was further analyzed by agarose gel electrophoresis, as shown in Figure 8. It was found that Fe3O4@SiO2 cannot bind VEGF shRNA, neither in deionized water nor in 0.9% NaCl solution (Figure 8A and B). This is due to the fact that both Fe3O4@SiO2 nanoparticles and DNA presented negative potential. However, for the same weight of nanoparticles, the surface charge is significantly higher after coating with PEI, which would provide a high adsorption capacity. As shown in Figure 8C, at different weight ratios from 5:1–40:1, the binding capability of Fe3O4@SiO2/PEI to VEGF shRNA enhanced with the weight ratio, and it increased in deionized water. When the weight ratio was over 30:1, almost all the VEGF shRNA was restrained with the nanocomposites. Consistent results were obtained when Fe3O4@SiO2/PEI/VEGF shRNA was incubated in 0.9% NaCl solution (Figure 8D). These data indicated that Fe3O4@SiO2/PEI nanoparticles were capable of effectively binding VEGF shRNA, and could be employed as a gene delivery carrier.


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)

Agarose gel electrophoresis retardation assays.Notes: (A) Fe3O4@SiO2:VEGF shRNA and (C) Fe3O4@SiO2/PEI:VEGF shRNA at different weight ratios (5:1, 10:1, 20:1, 30:1, and 40:1) in water; and (B) Fe3O4@SiO2:VEGF shRNA and (D) Fe3O4@SiO2/PEI:VEGF shRNA at different weight ratios (5:1, 10:1, 20:1, 30:1, and 40:1) in 0.9% NaCl.Abbreviations: shRNA, small hairpin RNA; PEI, polyethylenimine.
© Copyright Policy
Related In: Results  -  Collection

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

f8-ijn-10-4279: Agarose gel electrophoresis retardation assays.Notes: (A) Fe3O4@SiO2:VEGF shRNA and (C) Fe3O4@SiO2/PEI:VEGF shRNA at different weight ratios (5:1, 10:1, 20:1, 30:1, and 40:1) in water; and (B) Fe3O4@SiO2:VEGF shRNA and (D) Fe3O4@SiO2/PEI:VEGF shRNA at different weight ratios (5:1, 10:1, 20:1, 30:1, and 40:1) in 0.9% NaCl.Abbreviations: shRNA, small hairpin RNA; PEI, polyethylenimine.
Mentions: The nuclear acid-binding capability of the nanoparticles is a very important factor to consider when choosing a gene delivery carrier.41,42 The binding capacity to VEGF shRNA was further analyzed by agarose gel electrophoresis, as shown in Figure 8. It was found that Fe3O4@SiO2 cannot bind VEGF shRNA, neither in deionized water nor in 0.9% NaCl solution (Figure 8A and B). This is due to the fact that both Fe3O4@SiO2 nanoparticles and DNA presented negative potential. However, for the same weight of nanoparticles, the surface charge is significantly higher after coating with PEI, which would provide a high adsorption capacity. As shown in Figure 8C, at different weight ratios from 5:1–40:1, the binding capability of Fe3O4@SiO2/PEI to VEGF shRNA enhanced with the weight ratio, and it increased in deionized water. When the weight ratio was over 30:1, almost all the VEGF shRNA was restrained with the nanocomposites. Consistent results were obtained when Fe3O4@SiO2/PEI/VEGF shRNA was incubated in 0.9% NaCl solution (Figure 8D). These data indicated that Fe3O4@SiO2/PEI nanoparticles were capable of effectively binding VEGF shRNA, and could be employed as a gene delivery carrier.

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