Proteolytic nanoparticles enhance the penetration of drugs into pancreatic tumors

Assaf Zinger ¹ Omer Adir ¹ Maria Poley ¹ Lilach Koren ¹ Ofir Sivan ¹ Nadav Noor ⁶ Assaf Simon ¹ Hadas Gibori ² Janna Shainsky ¹ Yoav Binenbaum ³ Eran Fridman ³ Neta Milman ³ Michael Luebtow ⁴ Lior Liba ⁵ Dov Hershkovitz ⁷ Ziv Gil ³ Tal Dvir ⁶ Robert Luxenhofer ⁴ Ronit Satchi-Fainaro ² Avi Schroeder ¹

¹Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Chemical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
²Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv, Israel
³Department of Otolaryngology Head and Neck Surgery, Rambam Healthcare Campus, Haifa, Israel
⁴Functional Polymer Materials, Lehrstuhl für Chemische Technologie der Materialsynthese, 14 Julius-Maximilians-Universität Würzburg, Würzburg, Germany
⁵The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
⁶The School for Molecular Cell Biology and Biotechnology and the Department of Materials Science and Engineering, Tel Aviv University, Tel Aviv, Israel
⁷Department of Pathology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel

Pancreatic Ductal Adenocarcinoma (PDA) is the 4th leading cause of cancer related death in the United States alone. It is an extremely lethal cancer with less than 5% five-year survival rate. Surgical Resection is currently the only treatment with a chance of long term survival, however only 20% of the tumors are detected at a resectable stage and eventually many of patients re-develop this disease or metastatic disease. The development of a dense extracellular matrix barrier throughout the tumor reduces the efficiency of different treatment regimens. In this research, we sought to develop a drug delivery system that combines the field of enzymes and nanoparticle therapies. The system we developed releases Collagenase type-I at therapeutic concentrations in order to disassemble the PDA`s extracellular matrix. This will allow to improve the nanotherapeutics uptake and therapeutic efficacy at the tumor site.