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https://hdl.handle.net/2440/115633
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Type: | Journal article |
Title: | Histone deacetylase inhibitors delivery using nanoparticles with intrinsic passive tumor targeting properties for tumor therapy |
Author: | Bahhaj, F.E. Denis, I. Pichavant, L. Delatouche, R. Collette, F. Linot, C. Pouliquen, D. Grégoire, M. Héroguez, V. Blanquart, C. Bertrand, P. |
Citation: | Theranostics, 2016; 6(6):795-807 |
Publisher: | Ivyspring International |
Issue Date: | 2016 |
ISSN: | 1838-7640 1838-7640 |
Statement of Responsibility: | Fatima el Bahhaj, Iza Denis, Loic Pichavant, Régis Delatouche, Floraine Collette, Camille Linot, Daniel Pouliquen, Marc Grégoire, Valérie Héroguez, Christophe Blanquart, Philippe Bertrand |
Abstract: | 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 |
Rights: | © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions. |
DOI: | 10.7150/thno.13725 |
Published version: | http://dx.doi.org/10.7150/thno.13725 |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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hdl_115633.pdf | Published Version | 1.58 MB | Adobe PDF | View/Open |
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