SAVEME · A Modular Nanosystems Platform for Advanced Cancer Management: Nano-vehicles; Tumor Targeting and Penetration Agents; Molecular Imaging, Degradome based Therapy

SaveMe project will address current urgent needs for pancreatic cancer diagnosis and treatment by exploiting partners’ expertise and most recent research achievements for the design and development of novel modular nanosystems platform integrating new functionalized nano-core particles and active agents. The modular platform will enable the design of diverse active nanosystems per diagnostic or therapeutic application as defined by their active agent compositions. For diagnostics, superior tracers will be developed for molecular MR/PET and gamma camera imaging, enabling efficient diagnosis and guided surgery respectively. Novel functionalized nano-core systems will be conjugated with semi-confluent active shell layer. Three types of shell layers will be design: (1) novel iron oxide nanoparticles as advanced MRI contrast agents and/or (2) DOTA complexes for MRI (with Gd3+), or PET (with Ga-68), or gamma camera (with Ga-69); (3) Integrating within one tracer both iron oxide nanoparticles and DOTA-Ga-68 complexes for a sequential or simultaneous MR/PET imaging. For therapeutics, active nanosystems will be developed to deliver (1) therapeutic siRNAs or (2) anti-MP-inhibitory-scFVs. These non-classic anti-tumor drugs will be designed based on an extensive tumor degradome analysis for combining blockage of selective matrix MPs, thus preventing basic invasive and metastasis steps, with siRNA based neutralization of secondary molecular effects induced by the specific protease inhibition. Individualized degradome analysis will be developed for potential profiling of anti-MP and siRNAs based therapy per patient. To facilitate the above diagnostics and therapeutic effects, advanced tumor targeting and penetration active agents will be linked to nano-core functionalized groups, including a biocompatible PEG layer linked to tumor selective MMP substrate molecules and highly safe and potent novel somatostatin analogue peptides targeting SSTR overexpression.