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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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Magnetically targeted delivery of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex.(A) Photos of MDA-MB-231 cells incubated with Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex in the presence of a magnet. (B) Cellular uptake of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex (green) at different positions of the cell culture dish as indicated. (C) Fluorescence images of calcein-AM (green)/PI (red) double-stained cells at different positions of the cell culture dish as indicated. The number of cells showing both uptake of the nanoparticles and apoptosis near the magnet were significantly higher than that of cells far away from the magnet.
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f13: Magnetically targeted delivery of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex.(A) Photos of MDA-MB-231 cells incubated with Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex in the presence of a magnet. (B) Cellular uptake of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex (green) at different positions of the cell culture dish as indicated. (C) Fluorescence images of calcein-AM (green)/PI (red) double-stained cells at different positions of the cell culture dish as indicated. The number of cells showing both uptake of the nanoparticles and apoptosis near the magnet were significantly higher than that of cells far away from the magnet.

Mentions: Besides the folate receptor-mediated molecular targeting, the magnetic property of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex could be also utilized for magnetically targeted delivery. When MDA-MB-231 cells were incubated with Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex for 6 h, instead of 72 h for apoptosis assay, in the presence of a magnetic field under the center of the cell culture dish (Figure 13A), the uptake of the nanoparticles (green cells) by cells near the magnet was significantly higher than those far from the magnet (Figure 13B). Accordingly, the cells near the magnet showed apoptotic phenotype (red) compared to those far from the magnet (Figure 13C). Collectively, our data demonstrated that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex is an efficient gene delivery system possessing both molecular targeting and magnetic targeting capabilities.


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)

Magnetically targeted delivery of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex.(A) Photos of MDA-MB-231 cells incubated with Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex in the presence of a magnet. (B) Cellular uptake of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex (green) at different positions of the cell culture dish as indicated. (C) Fluorescence images of calcein-AM (green)/PI (red) double-stained cells at different positions of the cell culture dish as indicated. The number of cells showing both uptake of the nanoparticles and apoptosis near the magnet were significantly higher than that of cells far away from the magnet.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f13: Magnetically targeted delivery of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex.(A) Photos of MDA-MB-231 cells incubated with Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex in the presence of a magnet. (B) Cellular uptake of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex (green) at different positions of the cell culture dish as indicated. (C) Fluorescence images of calcein-AM (green)/PI (red) double-stained cells at different positions of the cell culture dish as indicated. The number of cells showing both uptake of the nanoparticles and apoptosis near the magnet were significantly higher than that of cells far away from the magnet.
Mentions: Besides the folate receptor-mediated molecular targeting, the magnetic property of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex could be also utilized for magnetically targeted delivery. When MDA-MB-231 cells were incubated with Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex for 6 h, instead of 72 h for apoptosis assay, in the presence of a magnetic field under the center of the cell culture dish (Figure 13A), the uptake of the nanoparticles (green cells) by cells near the magnet was significantly higher than those far from the magnet (Figure 13B). Accordingly, the cells near the magnet showed apoptotic phenotype (red) compared to those far from the magnet (Figure 13C). Collectively, our data demonstrated that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex is an efficient gene delivery system possessing both molecular targeting and magnetic targeting capabilities.

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