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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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Cell proliferation assay of human breast cancer MDA-MB-231 cells treated with Fe3O4@SiO2(FITC) (control), Fe3O4@SiO2(FITC)/PEI/Notch-1 shRNA (NPs/PEI/shRNA), Fe3O4@SiO2(FITC)/PEI/scrambled shRNA (NPs/PEI/SC), Fe3O4@SiO2(FITC)/PEI-FA/scrambled shRNA (NPs/PEI-FA/SC), or Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA (NPs/PEI-FA/shRNA).*p < 0.05 compared with control.
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f11: Cell proliferation assay of human breast cancer MDA-MB-231 cells treated with Fe3O4@SiO2(FITC) (control), Fe3O4@SiO2(FITC)/PEI/Notch-1 shRNA (NPs/PEI/shRNA), Fe3O4@SiO2(FITC)/PEI/scrambled shRNA (NPs/PEI/SC), Fe3O4@SiO2(FITC)/PEI-FA/scrambled shRNA (NPs/PEI-FA/SC), or Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA (NPs/PEI-FA/shRNA).*p < 0.05 compared with control.

Mentions: We then investigated whether these nanoparticles have any effect on cell proliferation. Cells were treated with various nanoparticles for 24, 48 and 72 h, and it showed that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex inhibited MDA-MB-231 cell proliferation, especially at 48 and 72 h (Figure 11). To evaluate whether the inhibition of cell proliferation by Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex was due to its apoptotic effect, the cell apoptosis was evaluated by calcein-AM/PI double staining. As shown in Figure 12, more cell apoptotic cells were observed in cells treated with Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex compared to control treatment. These data suggest that the inhibited cell proliferation induced by Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex was at least partially attributed to its apoptotic effect. Notch-1 signaling pathway is an evolutionarily conserved signaling pathway that has been shown to regulate many cellular processes including cell proliferation, differentiation, apoptosis, and survival4142. In light of the previous finding that silencing Notch-1 promoted cancer cell apoptosis2442, our data indicate that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex can be used as an efficient gene carrier for targeted killing of cancer cells bearing folate receptor.


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)

Cell proliferation assay of human breast cancer MDA-MB-231 cells treated with Fe3O4@SiO2(FITC) (control), Fe3O4@SiO2(FITC)/PEI/Notch-1 shRNA (NPs/PEI/shRNA), Fe3O4@SiO2(FITC)/PEI/scrambled shRNA (NPs/PEI/SC), Fe3O4@SiO2(FITC)/PEI-FA/scrambled shRNA (NPs/PEI-FA/SC), or Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA (NPs/PEI-FA/shRNA).*p < 0.05 compared with control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f11: Cell proliferation assay of human breast cancer MDA-MB-231 cells treated with Fe3O4@SiO2(FITC) (control), Fe3O4@SiO2(FITC)/PEI/Notch-1 shRNA (NPs/PEI/shRNA), Fe3O4@SiO2(FITC)/PEI/scrambled shRNA (NPs/PEI/SC), Fe3O4@SiO2(FITC)/PEI-FA/scrambled shRNA (NPs/PEI-FA/SC), or Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA (NPs/PEI-FA/shRNA).*p < 0.05 compared with control.
Mentions: We then investigated whether these nanoparticles have any effect on cell proliferation. Cells were treated with various nanoparticles for 24, 48 and 72 h, and it showed that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex inhibited MDA-MB-231 cell proliferation, especially at 48 and 72 h (Figure 11). To evaluate whether the inhibition of cell proliferation by Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex was due to its apoptotic effect, the cell apoptosis was evaluated by calcein-AM/PI double staining. As shown in Figure 12, more cell apoptotic cells were observed in cells treated with Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex compared to control treatment. These data suggest that the inhibited cell proliferation induced by Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex was at least partially attributed to its apoptotic effect. Notch-1 signaling pathway is an evolutionarily conserved signaling pathway that has been shown to regulate many cellular processes including cell proliferation, differentiation, apoptosis, and survival4142. In light of the previous finding that silencing Notch-1 promoted cancer cell apoptosis2442, our data indicate that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex can be used as an efficient gene carrier for targeted killing of cancer cells bearing folate receptor.

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