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Multifunctional core/shell nanoparticles cross-linked polyetherimide-folic acid as efficient Notch-1 siRNA carrier for targeted killing of breast cancer.

Yang H, Li Y, Li T, Xu M, Chen Y, Wu C, Dang X, Liu Y - Sci Rep (2014)

Bottom Line: Our results showed that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanoparticles are 64 nm in diameter with well dispersed and superparamagnetic.Magnetic resonance (MR) imaging and fluorescence microscopy showed significant preferential uptake of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex by MDA-MB-231 cells.Transfected MDA-MB-231 cells exhibited significantly decreased expression of Notch-1, inhibited cell proliferation, and increased cell apoptosis, leading to the killing of MDA-MB-231 cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, P.R. China.

ABSTRACT
In gene therapy, how genetic therapeutics can be efficiently and safely delivered into target tissues/cells remains a major obstacle to overcome. To address this issue, nanoparticles consisting of non-covalently coupled polyethyleneimine (PEI) and folic acid (FA) to the magnetic and fluorescent core/shell of Fe3O4@SiO2(FITC) was tested for their ability to deliver Notch-1 shRNA. Our results showed that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanoparticles are 64 nm in diameter with well dispersed and superparamagnetic. These nanoparticles with on significant cytotoxicity are capable of delivering Notch-1 shRNA into human breast cancer MDA-MB-231 cells with high efficiency while effectively protected shRNA from degradation by exogenous DNaseI and nucleases. Magnetic resonance (MR) imaging and fluorescence microscopy showed significant preferential uptake of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex by MDA-MB-231 cells. Transfected MDA-MB-231 cells exhibited significantly decreased expression of Notch-1, inhibited cell proliferation, and increased cell apoptosis, leading to the killing of MDA-MB-231 cells. In light of the magnetic targeting capabilities of Fe3O4@SiO2(FITC)/PEI-FA, our results show that by complexing with a second molecular targeting therapeutic, such as Notch-1 shRNA in this report, Fe3O4@SiO2(FITC)/PEI-FA can be exploited as a novel, non-viral, and concurrent targeting delivery system for targeted gene therapy as well as for MR imaging in cancer diagnosis.

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T2-weighted imaging of MDA-MB-231 cells.(A) MR images of phantoms containing MDA-MB-231 cells after 6 h incubation with Fe3O4@SiO2(FITC) (NPs), Fe3O4@SiO2(FITC)/PEI (NPs/PEI), Fe3O4@SiO2(FITC)/PEI-FA (NPs/PEI-FA) or Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA (NPs/PEI-FA/shRNA) at a concentration of 25.6 μg/ml. (B) T2-weighted MR images of Fe3O4@SiO2(FITC)/PEI/Notch-1 shRNA nanocomplex aqueous solutions at different Fe concentrations. A saline solution without any nanoparticles was used as the control group.
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f14: T2-weighted imaging of MDA-MB-231 cells.(A) MR images of phantoms containing MDA-MB-231 cells after 6 h incubation with Fe3O4@SiO2(FITC) (NPs), Fe3O4@SiO2(FITC)/PEI (NPs/PEI), Fe3O4@SiO2(FITC)/PEI-FA (NPs/PEI-FA) or Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA (NPs/PEI-FA/shRNA) at a concentration of 25.6 μg/ml. (B) T2-weighted MR images of Fe3O4@SiO2(FITC)/PEI/Notch-1 shRNA nanocomplex aqueous solutions at different Fe concentrations. A saline solution without any nanoparticles was used as the control group.

Mentions: To evaluate the potential of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex to be used as a targeted MR contrast agent, MDA-MB-231 cells were cultured with Fe3O4@SiO2(FITC), Fe3O4@SiO2(FITC)/PEI, Fe3O4@SiO2(FITC)/PEI-FA or Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA as described in materials and methods. Cells were harvested and resuspended in PBS and the T2-weighted MR phantom images were obtained. As shown in Figure 14, cells incubated with Fe3O4@SiO2(FITC)/PEI-FA or Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA showed a significant negative contrast enhancement (signal darkening) over other cells. As the concentration of the Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex increases, the T2-weighted MR image becomes darker for MDA-MB-231 cells, suggesting that the nanocomplex could also be used as a probe for T2 MR imaging. Our data demonstrated that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex can be exploited as a novel theranostic for cancer gene therapy and imaging probe for cancer diagnosis.


Multifunctional core/shell nanoparticles cross-linked polyetherimide-folic acid as efficient Notch-1 siRNA carrier for targeted killing of breast cancer.

Yang H, Li Y, Li T, Xu M, Chen Y, Wu C, Dang X, Liu Y - Sci Rep (2014)

T2-weighted imaging of MDA-MB-231 cells.(A) MR images of phantoms containing MDA-MB-231 cells after 6 h incubation with Fe3O4@SiO2(FITC) (NPs), Fe3O4@SiO2(FITC)/PEI (NPs/PEI), Fe3O4@SiO2(FITC)/PEI-FA (NPs/PEI-FA) or Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA (NPs/PEI-FA/shRNA) at a concentration of 25.6 μg/ml. (B) T2-weighted MR images of Fe3O4@SiO2(FITC)/PEI/Notch-1 shRNA nanocomplex aqueous solutions at different Fe concentrations. A saline solution without any nanoparticles was used as the control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4233336&req=5

f14: T2-weighted imaging of MDA-MB-231 cells.(A) MR images of phantoms containing MDA-MB-231 cells after 6 h incubation with Fe3O4@SiO2(FITC) (NPs), Fe3O4@SiO2(FITC)/PEI (NPs/PEI), Fe3O4@SiO2(FITC)/PEI-FA (NPs/PEI-FA) or Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA (NPs/PEI-FA/shRNA) at a concentration of 25.6 μg/ml. (B) T2-weighted MR images of Fe3O4@SiO2(FITC)/PEI/Notch-1 shRNA nanocomplex aqueous solutions at different Fe concentrations. A saline solution without any nanoparticles was used as the control group.
Mentions: To evaluate the potential of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex to be used as a targeted MR contrast agent, MDA-MB-231 cells were cultured with Fe3O4@SiO2(FITC), Fe3O4@SiO2(FITC)/PEI, Fe3O4@SiO2(FITC)/PEI-FA or Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA as described in materials and methods. Cells were harvested and resuspended in PBS and the T2-weighted MR phantom images were obtained. As shown in Figure 14, cells incubated with Fe3O4@SiO2(FITC)/PEI-FA or Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA showed a significant negative contrast enhancement (signal darkening) over other cells. As the concentration of the Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex increases, the T2-weighted MR image becomes darker for MDA-MB-231 cells, suggesting that the nanocomplex could also be used as a probe for T2 MR imaging. Our data demonstrated that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex can be exploited as a novel theranostic for cancer gene therapy and imaging probe for cancer diagnosis.

Bottom Line: Our results showed that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanoparticles are 64 nm in diameter with well dispersed and superparamagnetic.Magnetic resonance (MR) imaging and fluorescence microscopy showed significant preferential uptake of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex by MDA-MB-231 cells.Transfected MDA-MB-231 cells exhibited significantly decreased expression of Notch-1, inhibited cell proliferation, and increased cell apoptosis, leading to the killing of MDA-MB-231 cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, P.R. China.

ABSTRACT
In gene therapy, how genetic therapeutics can be efficiently and safely delivered into target tissues/cells remains a major obstacle to overcome. To address this issue, nanoparticles consisting of non-covalently coupled polyethyleneimine (PEI) and folic acid (FA) to the magnetic and fluorescent core/shell of Fe3O4@SiO2(FITC) was tested for their ability to deliver Notch-1 shRNA. Our results showed that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanoparticles are 64 nm in diameter with well dispersed and superparamagnetic. These nanoparticles with on significant cytotoxicity are capable of delivering Notch-1 shRNA into human breast cancer MDA-MB-231 cells with high efficiency while effectively protected shRNA from degradation by exogenous DNaseI and nucleases. Magnetic resonance (MR) imaging and fluorescence microscopy showed significant preferential uptake of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex by MDA-MB-231 cells. Transfected MDA-MB-231 cells exhibited significantly decreased expression of Notch-1, inhibited cell proliferation, and increased cell apoptosis, leading to the killing of MDA-MB-231 cells. In light of the magnetic targeting capabilities of Fe3O4@SiO2(FITC)/PEI-FA, our results show that by complexing with a second molecular targeting therapeutic, such as Notch-1 shRNA in this report, Fe3O4@SiO2(FITC)/PEI-FA can be exploited as a novel, non-viral, and concurrent targeting delivery system for targeted gene therapy as well as for MR imaging in cancer diagnosis.

Show MeSH
Related in: MedlinePlus