DataVXACS NanoPaper
journal article·2019-10-22Open access

Collagenase Nanoparticles Enhance the Penetration of Drugs into Pancreatic Tumors

Assaf Zinger, Lilach Koren, Omer Adir, Maria Poley, Mohammed Alyan, Zvi Yaari, Nadav Noor, Nitzan Krinsky, Assaf Simon, Hadas Gibori, Majd Krayem, Yelena Mumblat, Shira Kasten, Sivan Ofir, Eran Fridman, Neta Milman, Michael M. Lübtow, Lior Liba, Jeny Shklover, Janna Shainsky-Roitman, Yoav Binenbaum, Dov Hershkovitz, Ziv Gil, Tal Dvir, Robert Luxenhofer, Ronit Satchi-Fainaro, Avi Schroeder

ACS Nano· Volume 13· Issue 10
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Source abstract

Abstract

Overexpressed extracellular matrix (ECM) in pancreatic ductal adenocarcinoma (PDAC) limits drug penetration into the tumor and is associated with poor prognosis. Here, we demonstrate that a pretreatment based on a proteolytic-enzyme nanoparticle system disassembles the dense PDAC collagen stroma and increases drug penetration into the pancreatic tumor. More specifically, the collagozome, a 100 nm liposome encapsulating collagenase, was rationally designed to protect the collagenase from premature deactivation and prolonged its release rate at the target site. Collagen is the main component of the PDAC stroma, reaching 12.8 ± 2.3% vol in diseased mice pancreases, compared to 1.4 ± 0.4% in healthy mice. Upon intravenous injection of the collagozome, ∼1% of the injected dose reached the pancreas over 8 h, reducing the level of fibrotic tissue to 5.6 ± 0.8%. The collagozome pretreatment allowed increased drug penetration into the pancreas and improved PDAC treatment. PDAC tumors, pretreated with the collagozome followed by paclitaxel micelles, were 87% smaller than tumors pretreated with empty liposomes followed by paclitaxel micelles. Interestingly, degrading the ECM did not increase the number of circulating tumor cells or metastasis. This strategy holds promise for degrading the extracellular stroma in other diseases as well, such as liver fibrosis, enhancing tissue permeability before drug administration.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Pancreatic and Hepatic Oncology Research · Nanoparticle-Based Drug Delivery · Pancreatitis Pathology and Treatment

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion−Israel Institute of Technology, Haifa 3200003, Israel

The School for Molecular Cell Biology and Biotechnology and the Department of Materials Science and Engineering, Tel Aviv University, Tel Aviv 6997800, Israel

Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997800, Israel

Department of Otolaryngology Head and Neck Surgery, Rambam Healthcare Campus, Technion−Israel Institute of Technology, Haifa 3200000, Israel

Functional Polymer Materials, Lehrstuhl für Chemische Technologie der Materialsynthese, Julius-Maximilians-Universität Würzburg, Röntgenring 11, Würzburg 97070, Germany

The Ruth and Bruce Rappaport Faculty of Medicine, Technion−Israel Institute of Technology, Haifa 3200003, Israel

Department of Pathology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997800, Israel

Funding

Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion-Israel Institute of Technology · Israel Cancer Association · Technion-Israel Institute of Technology · Israel Science Foundation · German-Israeli Foundation for Scientific Research and Development · Rothschild Caesarea Foundation · Ministry of Science and Technology, Israel · Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology · H2020 European Research Council · Seventh Framework Programme · Technion Integrated Cancer Center, Technion-Israel Institute of Technology · Ministry of Economy of Israel · Mallat Family Foundation · Phospholipid Research Center

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