title: Functionalized Mesoporous Silica Nanoparticle with Antioxidants as a New Carrier That Generates Lower Oxidative Stress Impact on Cells.
abstract: Mesoporous silica nanoparticles (MSNs) were covalently coated with antioxidant molecules, namely, caffeic acid (MSN-CAF) or rutin (MSN-RUT), in order to diminish the impact of oxidative stress induced after transfection into cells, thus generating safer carriers used for either drug delivery or other applications. Two cellular models involved in the entry of NPs in the body were used for this purpose: the intestinal Caco-2 and the epidermal HaCaT cell lines. Rutin gave the best results in terms of antioxidant capacities preservation during coupling procedures, cellular toxicity alleviation, and decrease of ROS level after 24 h incubation of cells with grafted nanoparticles. These protective effects of rutin were found more pronounced in HaCaT than in Caco-2 cells, indicating some cellular specificity toward defense against oxidative stress. In order to gain more insight about the Nrf2 response, a stable transfected HaCaT cell line bearing repeats of the antioxidant response element (ARE) in front of a luciferase reporter gene was generated. In this cell line, both tBHQ and quercetin (Nrf2 agonists), but not rutin, were able to induce, in a dose-dependent fashion, the luciferase response. Interestingly, at high concentration, MSN-RUT was able to induce a strong Nrf2 protective response in HaCaT cells, accompanied by a comparable induction of HO-1 mRNA. The level of these responses was again less important in Caco-2 cells. To conclude, in keratinocyte cell line, the coupling of rutin to silica nanoparticles was beneficial in term of ROS reduction, cellular viability, and protective effects mediated through the activation of the Nrf2 antioxidant pathway.
authors.affiliation: PhyMedExp, Université de Montpellier , INSERM U1046, CNRS UMR 9214, 34295 Montpellier cedex 5, France.
authors.forename: Raymond
authors.initials: R
authors.lastname: Ebabe Elle
authors.affiliation: Institut Charles Gerhardt de Montpellier (ICGM), CNRS UMR 5253, Université de Montpellier , Campus Triolet, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France.
authors.forename: Saher
authors.initials: S
authors.lastname: Rahmani
authors.affiliation: PhyMedExp, Université de Montpellier , INSERM U1046, CNRS UMR 9214, 34295 Montpellier cedex 5, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Lauret
authors.affiliation: PhyMedExp, Université de Montpellier , INSERM U1046, CNRS UMR 9214, 34295 Montpellier cedex 5, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Morena
authors.affiliation: INRA, UMR AGAP, Centre de Recherche de Montpellier , 2 Place Pierre Viala-Bât. 21, 34060 Montpellier, France.
authors.forename: Luc Philippe Régis
authors.initials: LP
authors.lastname: Bidel
authors.affiliation: IRCM, Institut de Recherche en Cancérologie de Montpellier; INSERM, U1194; ICM Val d'Aurelle Paul Lamarque , Montpellier F-34298, France.
authors.forename: Abdelhay
authors.initials: A
authors.lastname: Boulahtouf
authors.affiliation: IRCM, Institut de Recherche en Cancérologie de Montpellier; INSERM, U1194; ICM Val d'Aurelle Paul Lamarque , Montpellier F-34298, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Balaguer
authors.affiliation: PhyMedExp, Université de Montpellier , INSERM U1046, CNRS UMR 9214, 34295 Montpellier cedex 5, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Cristol
authors.affiliation: Institut Charles Gerhardt de Montpellier (ICGM), CNRS UMR 5253, Université de Montpellier , Campus Triolet, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France.
authors.forename: Jean-Olivier
authors.initials: JO
authors.lastname: Durand
authors.affiliation: Institut Charles Gerhardt de Montpellier (ICGM), CNRS UMR 5253, Université de Montpellier , Campus Triolet, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France.
authors.forename: Clarence
authors.initials: C
authors.lastname: Charnay
authors.affiliation: PhyMedExp, Université de Montpellier , INSERM U1046, CNRS UMR 9214, 34295 Montpellier cedex 5, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Badia
mesh_terms: D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D018938:Caco-2 Cells; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006873:Hydroquinones / Q000737:chemistry / Q000494:pharmacology; D051267:NF-E2-Related Factor 2 / Q000819:agonists / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D016133:Polymerase Chain Reaction; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D002396:Catechols; D006873:Hydroquinones; D051267:NF-E2-Related Factor 2; D012822:Silicon Dioxide; D011794:Quercetin; C018855:2-tert-butylhydroquinone; C034221:catechol
keywords: Caco-2 cell line; HaCaT cell line; Nrf2; antioxidative response; catechol antioxidant; mesoporous silica nanoparticle