Please use this identifier to cite or link to this item: http://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
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.
RMID: 0030066012
DOI: 10.7150/thno.13725
Appears in Collections:Medicine publications

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