Endocrine Abstracts (2016) 40 OC3 | DOI: 10.1530/endoabs.40.OC3

Mesoporous silica nanoparticles for somatostatin targeted Notch activation in animal model of pancreatic neuroendocrine cancer

Valeriy M Paramonov1,2, Diti Desai3, Veronika Mamaeva4, Jessica Rosenholm3, Adolfo Rivero-Müller1,2,5,6 & Cecilia Sahlgren2,7


1Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland; 2Turku Center for Biotechnology, University of Turku and Æbo Akademi University, Turku, Finland; 3Pharmaceutical Sciences Laboratory, Æbo Akademi University, Turku, Finland; 4Department of Clinical Science, University of Bergen, Bergen, Norway; 5Faculty of Natural Sciences and Technology, Æbo Akademi University, Turku, Finland; 6Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland; 7Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.


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.

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