title: Viability and gene expression responses to polymeric nanoparticles in human and rat cells.
abstract: Applications of polymeric nanoparticles (NP) in medical fields are rapidly expanding. However, the influence of polymeric NP on cell growth and functions is widely underestimated. Therefore, we have studied cell and polymeric NP interactions by addressing two cell types with two endpoints (viability and gene expressions). Rat NR8383 and human THP-1 monocytic cell lines were exposed to 6 to 200 μg/mL of Eudragit(®) RL NP for 24 h, and cellular viability was estimated using MTT, WST-1, and trypan blue tests. A decrease of viability was observed with NR8383 cells (down to 70% for 200 μg/mL), and on the contrary, an increase with THP-1 cells (up to 140% for 200 μg/mL). Differential expression of genes involved in oxidative damage (NCF1), inflammation (NFKB, TNFA, IL6, IL1B), autophagy (ATG16L), and apoptotic balance (PDCD4, BCL2, CASP8) was analyzed. ATG16L, BCL2, and TNFA were up-regulated in NR8383 cells, which are consistent with an induction of autophagy and inflammation. On the other hand, NCF1, NFKB, and IL1B were down-regulated in THP-1 cells, which may contribute to explain the increase of cellular viability. Our results show that (1) the toxic potency of NP is dependent on the cellular model used and (2) mechanistic toxicology should be the corner stone for the evaluation of NP hazard.
authors.affiliation: Faculté de Pharmacie, EA 3452 CITHÉFOR, Université de Lorraine, 5 rue Albert Lebrun, 54000, Nancy, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Ronzani
authors.forename: Ramia
authors.initials: R
authors.lastname: Safar
authors.forename: Roudayna
authors.initials: R
authors.lastname: Diab
authors.forename: Jérôme
authors.initials: J
authors.lastname: Chevrier
authors.forename: Justine
authors.initials: J
authors.lastname: Paoli
authors.forename: Mosaad A
authors.initials: MA
authors.lastname: Abdel-Wahhab
authors.forename: Alain
authors.initials: A
authors.lastname: Le Faou
authors.forename: Bertrand H
authors.initials: BH
authors.lastname: Rihn
authors.forename: Olivier
authors.initials: O
authors.lastname: Joubert
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007249:Inflammation; D053758:Nanoparticles; D018384:Oxidative Stress / Q000187:drug effects*; D011109:Polymethacrylic Acids / Q000494:pharmacology*; D051381:Rats
chemical_list: D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer