title: Vorinostat-polymer conjugate nanoparticles for Acid-responsive delivery and passive tumor targeting.
abstract: In vivo histone deacetylase (HDAC) inhibition by vorinostat under clinically acceptable dosing is limited by its poor pharmacokinetics properties. A new type of nontoxic pH-responsive delivery system has been synthesized by ring-opening metathesis polymerization, allowing for the selective distribution of vorinostat in mesothelioma tumors in vivo and subsequent histone reacetylation. The delivery system is synthesized by generic click chemistry, possesses native stealth properties for passive tumor targeting, and does not need additional chemistry for cellular internalization. Although vorinostat alone at 50 mg/kg in mice showed no effect, our new delivery system with 2 mg/kg vorinostat promoted histone reacetylation in tumors without side effects, demonstrating that our strategy improves the activity of this HDAC inihibitor in vivo.
authors.affiliation: Inserm, UMR 892 , Nantes F-44000, France.
authors.forename: Iza
authors.initials: I
authors.lastname: Denis
authors.forename: Fatima
authors.initials: F
authors.lastname: El Bahhaj
authors.forename: Floraine
authors.initials: F
authors.lastname: Collette
authors.forename: Régis
authors.initials: R
authors.lastname: Delatouche
authors.forename: Fabien
authors.initials: F
authors.lastname: Gueugnon
authors.forename: Daniel
authors.initials: D
authors.lastname: Pouliquen
authors.forename: Loic
authors.initials: L
authors.lastname: Pichavant
authors.forename: Valérie
authors.initials: V
authors.lastname: Héroguez
authors.forename: Marc
authors.initials: M
authors.lastname: Grégoire
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertrand
authors.forename: Christophe
authors.initials: C
authors.lastname: Blanquart
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry; D016503:Drug Delivery Systems; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology*; D008654:Mesothelioma / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D014162:Transfection; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011108:Polymers; D000077337:Vorinostat