Histone deacetylase inhibitor-polymer conjugate nanoparticles for acid-responsive drug delivery
EL BAHHAJ, Fatima
Institut de chimie des milieux et matériaux de Poitiers [UMR 7285] [IC2MP [Poitiers]]
Institut de chimie des milieux et matériaux de Poitiers [UMR 7285] [IC2MP [Poitiers]]
COLLETTE, Floraine
Laboratoire de Chimie des Polymères Organiques [LCPO]
Team 1 LCPO : Polymerization Catalyses & Engineering
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Laboratoire de Chimie des Polymères Organiques [LCPO]
Team 1 LCPO : Polymerization Catalyses & Engineering
EL BAHHAJ, Fatima
Institut de chimie des milieux et matériaux de Poitiers [UMR 7285] [IC2MP [Poitiers]]
Institut de chimie des milieux et matériaux de Poitiers [UMR 7285] [IC2MP [Poitiers]]
COLLETTE, Floraine
Laboratoire de Chimie des Polymères Organiques [LCPO]
Team 1 LCPO : Polymerization Catalyses & Engineering
Laboratoire de Chimie des Polymères Organiques [LCPO]
Team 1 LCPO : Polymerization Catalyses & Engineering
DELATOUCHE, Régis
Institut de chimie des milieux et matériaux de Poitiers [UMR 7285] [IC2MP [Poitiers]]
Institut de chimie des milieux et matériaux de Poitiers [UMR 7285] [IC2MP [Poitiers]]
GUEUGNON, Fabien
Centre de Recherche en Cancérologie Nantes-Angers [CRCNA]
Université de Nantes [UN]
Centre de Recherche en Cancérologie Nantes-Angers [CRCNA]
Université de Nantes [UN]
POULIQUEN, Daniel
Centre de Recherche en Cancérologie Nantes-Angers [CRCNA]
Université de Nantes [UN]
Centre de Recherche en Cancérologie Nantes-Angers [CRCNA]
Université de Nantes [UN]
PICHAVANT, Loïc
Laboratoire de Chimie des Polymères Organiques [LCPO]
Team 1 LCPO : Polymerization Catalyses & Engineering
Laboratoire de Chimie des Polymères Organiques [LCPO]
Team 1 LCPO : Polymerization Catalyses & Engineering
HÉROGUEZ, Valérie
Laboratoire de Chimie des Polymères Organiques [LCPO]
Team 1 LCPO : Polymerization Catalyses & Engineering
Laboratoire de Chimie des Polymères Organiques [LCPO]
Team 1 LCPO : Polymerization Catalyses & Engineering
PHILIPPE, Bertrand
Institut de chimie des milieux et matériaux de Poitiers [UMR 7285] [IC2MP [Poitiers]]
Institut de chimie des milieux et matériaux de Poitiers [UMR 7285] [IC2MP [Poitiers]]
BLANQUART, Christophe
Centre de Recherche en Cancérologie Nantes-Angers [CRCNA]
Université de Nantes [UN]
< Réduire
Centre de Recherche en Cancérologie Nantes-Angers [CRCNA]
Université de Nantes [UN]
Langue
en
Article de revue
Ce document a été publié dans
European Journal of Medicinal Chemistry. 2015, vol. 95, p. 369-376
Elsevier
Résumé en anglais
We report the synthesis of acid responsive polymeric nanoparticles (NPs) consisting of a polymerhistone deacetylase inhibitor conjugate. An innovative aspect of this drug delivery particle lies in the NP conjugation of a ...Lire la suite >
We report the synthesis of acid responsive polymeric nanoparticles (NPs) consisting of a polymerhistone deacetylase inhibitor conjugate. An innovative aspect of this drug delivery particle lies in the NP conjugation of a histone deacetylase (HDAC) inhibitor, CI-994 (Tacedinaline), introduced with a clickable acid-responsive prodrug during monomer synthesis, prior to polymerization. Another novelty lies in the selected norbornene (NB)-polyethylene oxide (PEO) macromonomer allowing standardization of the polymerization process by Ring-Opening Metathesis Polymerization (ROMP) and functionalization through azide-allcyne click chemistry. Herein we demonstrate that the synthesized polymer gave 300 nm core-shell spherical nanoparticles with low dispersity (0.04), high water dispersability thanks to the PEO shell and well controlled HDAC inhibitor prodrug loading. Bioluminescence Resonance Energy Transfer (BRET) assay in living cells and viability experiments demonstrated efficient cellular internalization without additional chemistry, drug release inside cells with restoration of the HDAC inhibition and induction of apoptosis. Such NPs should minimize drug release in vivo during blood circulation and trigger intracellular delivery after endocytosis, holding promises for improved efficacy of this class of epigenetic inhibitors. This standardized synthesis paves the way for multifunctional nanoparticles synthesis.< Réduire
Mots clés en anglais
CI-994
CANCER
OXIDE)
Polymeric nanoparticle
Epigenetic inhibitor
Drug delivery
Controlled release
Stimuli-responsive
OPENING METATHESIS POLYMERIZATION
HDAC
Origine
Importé de halUnités de recherche