Figure 1.

Targeting Notch signaling by design. (a) Upon binding to Jagged or Delta ligands, the Notch receptor is subjected to proteolytic processing that releases the Notch intracellular domain (NICD), which translocates to the nucleus where it regulates Notch-dependent gene expression. The cleavage event is mediated by the γ-secretase (GS) complex rendering Notch sensitive to GS-inhibitors (GSIs). (b) For targeted Notch therapy, the following particle design was chosen: mesoporous silica nanoparticle (MSNP) matrix for loading of GSI; surface functionalization of a PEI-layer for facilitated further modifications such as coupling of targeting ligands, suspension stabilization, and possible molecular gate properties; labeling with fluorophore for easy visualization and conjugation of folate (FA) to the PEI-layer on the particle surface for cellular targeting. FITC, fluorescein isothiocyanate