Theranostics 2016; 6(6):795-807. doi:10.7150/thno.13725 This issue Cite
Research Paper
1. Institut de Chimie des Milieux et Matériaux de Poitiers, University of Poitiers, CNRS UMR 7285, 4 rue Michel Brunet TSA 51106, B27, Poitiers. F-86073 Poitiers cedex 9, France
2. Centre de Recherche contre le Cancer Nantes et Angers, University of Nantes, CNRS UMR 6299, Inserm, U892, 8 quai Moncousu, F-44000 Nantes cedex 1, France
3. Laboratoire de Chimie des Polymères Organiques, University of Bordeaux, CNRS UMR 5629, 16 Avenue Pey-Berland, F-33607 Pessac, France
4. Réseau Epigénétique du Cancéropôle Grand Ouest.
# These authors have equally contributed to this work.
* These authors have equally contributed to this work.
Fast clearance, metabolism and systemic toxicity are major limits for the clinical use of anti-cancer drugs. Histone deacetylase inhibitors (HDACi) present these defects despite displaying promising anti-tumor properties on tumor cells in vitro and in in vivo model of cancers. Specific delivery of anti-cancer drugs into the tumor should improve their clinical benefit by limiting systemic toxicity and by increasing the anti-tumor effect. In this work, we describe a simple and flexible polymeric nanoparticle platform highly targeting the tumor in vivo and triggering impressive tumor weight reduction when functionalized with HDACi. Our nanoparticles were produced by Ring-Opening Metathesis Polymerization of azido-polyethylene oxide-norbornene macromonomers and functionalized using click chemistry. Using an orthotopic model of peritoneal invasive cancer, a highly selective accumulation of the particles in the tumor was obtained. A combination of epigenetic drugs involving a pH-responsive histone deacetylase inhibitor (HDACi) polymer conjugated to these particles gave 80% reduction of tumor weight without toxicity whereas the free HDACi has no effect. Our work demonstrates that the use of a nanovector with theranostic properties leads to an optimized delivery of potent HDACi in tumor and then, to an improvement of their anti-tumor properties in vivo.
Keywords: polymeric nanoparticle, epigenetic, HDAC, cancer, theranostics, peritoneal, mesothelioma.