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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

Schematic illustrating the preparation of Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites for gene delivery.Notes: (A) Hydrolyzing TEOS to form the first silica shell; (B) hydrolyzing AEAP3 to form the second silica shell. (C) Coating PEI on the surface of Fe3O4@SiO2 nanoparticles (Fe3O4@SiO2/PEI); (D) binding of VEGF shRNA to Fe3O4@SiO2/PEI by electrostatic interaction (Fe3O4@SiO2/PEI/VEGF shRNA).Abbreviations: TEOS, tetraethylorthosilicate; AEAP3, N-(2-aminoethyl)-3-amino-propyltrimetho-xysilane; PEI, polyethylenimine; shRNA, small hairpin RNA.
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f1-ijn-10-4279: Schematic illustrating the preparation of Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites for gene delivery.Notes: (A) Hydrolyzing TEOS to form the first silica shell; (B) hydrolyzing AEAP3 to form the second silica shell. (C) Coating PEI on the surface of Fe3O4@SiO2 nanoparticles (Fe3O4@SiO2/PEI); (D) binding of VEGF shRNA to Fe3O4@SiO2/PEI by electrostatic interaction (Fe3O4@SiO2/PEI/VEGF shRNA).Abbreviations: TEOS, tetraethylorthosilicate; AEAP3, N-(2-aminoethyl)-3-amino-propyltrimetho-xysilane; PEI, polyethylenimine; shRNA, small hairpin RNA.

Mentions: PEI was coated on the surfaces of the Fe3O4@SiO2 nanoparticles through electrostatic interaction. Briefly, PEI solution (20 mg/mL) was added into the Fe3O4@SiO2 nanoparticle suspension (5 mg/mL), which was then mixed by stirring for 2 hours to allow PEI to graft onto the surfaces of the Fe3O4@SiO2 nanoparticles. Unbound PEI was removed by centrifugation with deionized water three times. The PEI-functionalized Fe3O4@SiO2 nanoparticles were harvested by centrifugation and washed five times with distilled water to remove excess reactants. VEGF shRNA was incubated in the Fe3O4@SiO2/PEI nanoparticle suspension for 30 minutes at room temperature to form Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites by electrostatic absorption at various weight ratios. The synthetic procedure for the Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites is summarized in Figure 1.


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)

Schematic illustrating the preparation of Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites for gene delivery.Notes: (A) Hydrolyzing TEOS to form the first silica shell; (B) hydrolyzing AEAP3 to form the second silica shell. (C) Coating PEI on the surface of Fe3O4@SiO2 nanoparticles (Fe3O4@SiO2/PEI); (D) binding of VEGF shRNA to Fe3O4@SiO2/PEI by electrostatic interaction (Fe3O4@SiO2/PEI/VEGF shRNA).Abbreviations: TEOS, tetraethylorthosilicate; AEAP3, N-(2-aminoethyl)-3-amino-propyltrimetho-xysilane; PEI, polyethylenimine; shRNA, small hairpin RNA.
© Copyright Policy
Related In: Results  -  Collection

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

f1-ijn-10-4279: Schematic illustrating the preparation of Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites for gene delivery.Notes: (A) Hydrolyzing TEOS to form the first silica shell; (B) hydrolyzing AEAP3 to form the second silica shell. (C) Coating PEI on the surface of Fe3O4@SiO2 nanoparticles (Fe3O4@SiO2/PEI); (D) binding of VEGF shRNA to Fe3O4@SiO2/PEI by electrostatic interaction (Fe3O4@SiO2/PEI/VEGF shRNA).Abbreviations: TEOS, tetraethylorthosilicate; AEAP3, N-(2-aminoethyl)-3-amino-propyltrimetho-xysilane; PEI, polyethylenimine; shRNA, small hairpin RNA.
Mentions: PEI was coated on the surfaces of the Fe3O4@SiO2 nanoparticles through electrostatic interaction. Briefly, PEI solution (20 mg/mL) was added into the Fe3O4@SiO2 nanoparticle suspension (5 mg/mL), which was then mixed by stirring for 2 hours to allow PEI to graft onto the surfaces of the Fe3O4@SiO2 nanoparticles. Unbound PEI was removed by centrifugation with deionized water three times. The PEI-functionalized Fe3O4@SiO2 nanoparticles were harvested by centrifugation and washed five times with distilled water to remove excess reactants. VEGF shRNA was incubated in the Fe3O4@SiO2/PEI nanoparticle suspension for 30 minutes at room temperature to form Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites by electrostatic absorption at various weight ratios. The synthetic procedure for the Fe3O4@SiO2/PEI/VEGF shRNA nanocomposites is summarized in Figure 1.

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