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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.


Related in: MedlinePlus

Magnetization curves of Fe3O4@SiO2 and Fe3O4@SiO2/PEI measured at room temperature.Notes: Inset: magnetic targeting under an external magnet, (A) Fe3O4@SiO2 and (B) Fe3O4@SiO2/PEI.Abbreviation: PEI, polyethylenimine.
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f5-ijn-10-4279: Magnetization curves of Fe3O4@SiO2 and Fe3O4@SiO2/PEI measured at room temperature.Notes: Inset: magnetic targeting under an external magnet, (A) Fe3O4@SiO2 and (B) Fe3O4@SiO2/PEI.Abbreviation: PEI, polyethylenimine.

Mentions: Figure 4 shows the zeta-potential titrations as a function of pH for Fe3O4@SiO2, Fe3O4@SiO2/PEI, and Fe3O4@ SiO2/PEI/VEGF shRNA nanocomposites. It was found that isoelectric points for Fe3O4@SiO2/PEI and Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites were increased to 9.7 and 10.5, respectively. The isoelectric points were increased as modified with polymer, and the shift of the isoelectric points indicated that the PEI modification and VEGF shRNA electrostatical absorption were successful.36–38 For the assessment of the magnetic properties and the sensitivity of the formulated nanoparticles, magnetic hysteresis loops were recorded using a magnetometer, and the two types of nanoparticles showed superparamagnetic behavior without magnetic hysteresis (Figure 5) at room temperature (about 300 K). PEI modification did not change the magnetic property of Fe3O4@SiO2 nanoparticles. Their magnetization saturation value was ~4.4 emu/g, and no significant difference in the magnetization saturation value was observed for the Fe3O4@SiO2 and Fe3O4@SiO2/PEI nanoparticles. Furthermore, the magnetic targeting of nanoparticles was tested in water by placing a magnet near the glass bottle. Both the Fe3O4@SiO2 and Fe3O4@SiO2/PEI were attracted toward the magnet within a very short period of time (Figure 5, inset). These data revealed their superparamagnetic nature, and the nanoparticles could also get to targeted locations under an external magnetic field.


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)

Magnetization curves of Fe3O4@SiO2 and Fe3O4@SiO2/PEI measured at room temperature.Notes: Inset: magnetic targeting under an external magnet, (A) Fe3O4@SiO2 and (B) Fe3O4@SiO2/PEI.Abbreviation: PEI, polyethylenimine.
© Copyright Policy
Related In: Results  -  Collection

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

f5-ijn-10-4279: Magnetization curves of Fe3O4@SiO2 and Fe3O4@SiO2/PEI measured at room temperature.Notes: Inset: magnetic targeting under an external magnet, (A) Fe3O4@SiO2 and (B) Fe3O4@SiO2/PEI.Abbreviation: PEI, polyethylenimine.
Mentions: Figure 4 shows the zeta-potential titrations as a function of pH for Fe3O4@SiO2, Fe3O4@SiO2/PEI, and Fe3O4@ SiO2/PEI/VEGF shRNA nanocomposites. It was found that isoelectric points for Fe3O4@SiO2/PEI and Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites were increased to 9.7 and 10.5, respectively. The isoelectric points were increased as modified with polymer, and the shift of the isoelectric points indicated that the PEI modification and VEGF shRNA electrostatical absorption were successful.36–38 For the assessment of the magnetic properties and the sensitivity of the formulated nanoparticles, magnetic hysteresis loops were recorded using a magnetometer, and the two types of nanoparticles showed superparamagnetic behavior without magnetic hysteresis (Figure 5) at room temperature (about 300 K). PEI modification did not change the magnetic property of Fe3O4@SiO2 nanoparticles. Their magnetization saturation value was ~4.4 emu/g, and no significant difference in the magnetization saturation value was observed for the Fe3O4@SiO2 and Fe3O4@SiO2/PEI nanoparticles. Furthermore, the magnetic targeting of nanoparticles was tested in water by placing a magnet near the glass bottle. Both the Fe3O4@SiO2 and Fe3O4@SiO2/PEI were attracted toward the magnet within a very short period of time (Figure 5, inset). These data revealed their superparamagnetic nature, and the nanoparticles could also get to targeted locations under an external magnetic field.

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