Functionalized Mesoporous Silica Nanoparticle with Antioxidants as a New Carrier That Generates Lower Oxidative Stress Impact on Cells

• Published in: Molecular pharmaceutics Vol. 13; no. 8; pp. 2647 - 2660
• Main Authors: Ebabe Elle, Raymond, Rahmani, Saher, Lauret, Céline, Morena, Marion, Bidel, Luc Philippe Régis, Boulahtouf, Abdelhay, Balaguer, Patrick, Cristol, Jean-Paul, Durand, Jean-Olivier, Charnay, Clarence, Badia, Eric
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01-08-2016
• Subjects: Antioxidants - chemistry; Antioxidants - pharmacology; Caco-2 Cells; Catechols - chemistry; Catechols - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Humans; Hydroquinones - chemistry; Hydroquinones - pharmacology; Life Sciences; Nanoparticles - chemistry; NF-E2-Related Factor 2 - agonists; NF-E2-Related Factor 2 - metabolism; Oxidative Stress - drug effects; Polymerase Chain Reaction; Quercetin - chemistry; Quercetin - pharmacology; Silicon Dioxide - chemistry; mesoporous silica nanoparticle; catechol antioxidant; Nrf2; HaCaT cell line; Caco-2 cell line; antioxidative response
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.6b00190

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.