Pancreatic neuroendocrine tumors (PNETs) form a distinct entity of malignant lesions with a dreadful prognosis. More than 50% of the patients already have distant metastasis by the time of diagnosis, which underpins the urgent need for more effective treatment modalities. Notch pathway, evolutionary old and highly cellular context dependent signalling mechanism, was shown to regulate growth and development of normal neuroendocrine cells and PNETs, with experimental data implying its function as a tumor suppressor gene in these malignancies. Development of nanoparticulate system for delivery of Notch activators directly to pNETs may solve the long-standing problem of unwanted systemic effects of such compounds. Our group & collaborators have engineered, synthesized and successfully tested mesoporous silica nanoparticles (MSNPs) in different cell lines and in a breast cancer animal model for Notch inhibitor delivery. PNETs, as unique tumors with repressed Notch pathway represent an appealing testing platform for nanocarrier-mediated Notch activator delivery. MSNPs, decorated with tumor-inhibiting somatostatin analogues and loaded with Notch activators, may make an elegant vehicle, selectively steering this tumoricidal cocktail to PNETs with inherently high levels of somatostatin receptors.