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. 2011 May 31;19(8):1538–1546. doi: 10.1038/mt.2011.105

Figure 2.

Figure 2

Cell-specific block of Notch signaling by γ-secretase inhibitor-mesoporous silica nanoparticles (GSI-MSNPs) conjugated to folate (FA). (a) Luciferase reporter assays for Notch activity demonstrate cell-specific inhibition of Notch in high- folate receptor (FR) HeLa cells as compared to low-FR 293 cells at 24 hours of incubation with MSNPs loaded with 1 weight% and 2.5 weight% GSI, respectively. Notch was activated by transfection of ΔE Notch1 in both cell lines. Control MSNPs (Ctrl-MSNPs) denote drug free control particles; GSI-MSNPs denote GSI-containing particles. Both particles were FA-conjugated. X-axis denotes particle concentration (n ≥ 3; mean ± SD). (b) Luciferase reporter assay demonstrates dose-dependent inhibition of Notch signaling by free GSI in 293 and HeLa cells (n ≥ 3; mean ± SD). The boxes in a and b denote GSI concentration at 0.1 µg/ml (***P < 0.0001). (c) Immunoblot of HeLa cells transfected with GS-cleavable active form of Notch, ΔENotch1, and treated with GSI-loaded (GSI-MSNPs) and drug free particles (Ctrl-MSNPs) using an antibody against the GS-cleaved active form of Notch, Notch intracellular domain (NICD). Hsc-70 is used as a loading control. RLU, relative luciferase units.