title: Drug delivery by polymeric nanoparticles induces autophagy in macrophages.
abstract: Drug delivery nanosystems are currently used in human therapy. In preliminary studies we have observed that Eudragit RS nanoparticles, prepared by nanoprecipitation or double emulsion techniques, are cytotoxic for NR8383 rat macrophages. In this study, we expand our previous analysis and suggest that unloaded Eudragit RS nanoparticles prepared by nanoprecipitation (NP/ERS) may induce important morphological and biochemical cellular modifications leading to cellular death. In NR8383 rat macrophages cell line exposed to doses varying from 15 to 100 μg/mL, NP/ERS nanoparticles are internalized inside the cells, reach the mitochondria and alter the structure of these organelles. In addition, the exposure to nanoparticles induces cellular autophagy as demonstrated by electron microscopy analysis, microchip array, qRT-PCR and Western blot assays. Although toxicity of nanoparticles has already been evidenced, it is the first time that results show clearly that the toxicity of polymeric nanovectors may be related to an activation of autophagy.
authors: Faculté de Pharmacie, EA 3452 CITHEFOR, Nancy-Université, 54001 Nancy Cedex, France.
authors: H
authors: H
authors: Eidi
authors: O
authors: O
authors: Joubert
authors: C
authors: C
authors: Némos
authors: S
authors: S
authors: Grandemange
authors: B
authors: B
authors: Mograbi
authors: B
authors: B
authors: Foliguet
authors: J
authors: J
authors: Tournebize
authors: P
authors: P
authors: Maincent
authors: A
authors: A
authors: Le Faou
authors: I
authors: I
authors: Aboukhamis
authors: B H
authors: BH
authors: Rihn
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004705:Endocytosis; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D053758:Nanoparticles; D036103:Nanotechnology; D020411:Oligonucleotide Array Sequence Analysis; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D004337:Drug Carriers; C496966:Eudragit RSPO; D011109:Polymethacrylic Acids; D017382:Reactive Oxygen Species; D005978:Glutathione