Size-Dependent Localization and Quantitative Evaluation of the Intracellular Migration of Silica Nanoparticles in Caco-2 Cells

Schübbe, Sabrina; Schümann, Christian; Cavelius, Christian; Koch, Marcus; Müller, Tobias; Kraegeloh, Annette

doi:10.1021/cm2018532

Cited by 50 publications

(37 citation statements)

References 61 publications

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“…Because silica NPs with food first pass through the gastrointestinal tract, thereafter they may be distributed to other organs, we first need to study the interaction of silica NPs with the gastrointestinal tract. However, previous studies involving the gastrointestinal tract are preliminary and limited (Gerloff et al, 2009;Moulari et al, 2008;Schubbe et al, 2012;Sergent et al, 2012). Thus, we performed this in-depth study in various aspects to understand the potential damage of food additive silica NPs to two model gastrointestinal cells, GES-1 and Caco-2 cells.…”

Section: Discussionmentioning

confidence: 99%

“…Several in vivo experiments show that silica NPs could enter the animal body through different exposure pathways and, distribute in nearly all organs and induce adverse effects in animals (Kaewamatawong et al, 2006;Nishimori et al, 2009;So et al, 2008;Xie et al, 2009). The relevant in vitro studies indicate that silica NPs are cytotoxic to various cell lines (Canesi et al, 2010;Cousins et al, 2004;Eom and Choi, 2009;Gerloff et al, 2009;Gualtieri et al, 2012;Li et al, 2011;Lin et al, 2006;Napierska et al, 2009;Perkins et al, 2012;Sergent et al, 2012;Schubbe et al, 2012), and the cytotoxicity depends on the exposure dose, exposure time and physicochemical properties of silica NPs, such as size and surface group. However, most cell studies were designed from the occupational exposure point of view, focusing primarily on pulmonary toxicity (Eom and Choi, 2009;Gualtieri et al, 2012;Li et al, 2011;Lin et al, 2006;Perkins et al, 2012); cytotoxicity studies on the silica NPs taken as a food ingredient are very limited (Dekkers et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…In general, food additive silica NPs enter the human gastrointestinal tract along with food by oral administration. At present, only a few studies have investigated gastrointestinal toxicity, including the toxicity of silica NPs to cell lines originating from the gastrointestinal tract (Gerloff et al, 2009;Gehrke et al, 2013;Schubbe et al, 2012;Sergent et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the toxicity of food additive silica nanoparticles on gastrointestinal cells

Yang

Zhang

Cheng

et al. 2013

J of Applied Toxicology

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Silica nanoparticles (NPs) have been widely used in food products as an additive; however, their toxicity and safety to the human body and the environment still remain unclear. As a food additive, silica NPs firstly enter the human gastrointestinal tract along with food, thus their gastrointestinal toxicity deserves thorough study. Herein, we evaluated the toxicity of food additive silica NPs to cells originating from the gastrointestinal tract. Four silica NP samples were introduced to human gastric epithelial cell GES-1 and colorectal adenocarcinoma cell Caco-2 to investigate the effect of silica sample, exposure dose and exposure period on the morphology, viability and membrane integrity of cells. The cell uptake, cellular reactive oxygen species (ROS) level, cell cycle and apoptosis were determined to reveal the toxicity mechanism. The results indicate that all four silica NPs are safe for both GES-1 and Caco-2 cells after 24-h exposure at a concentration lower than 100 µg ml(-1) . At a higher concentration and longer exposure period, silica NPs do not induce the apoptosis/necrosis of cells, but arrest cell cycle and inhibit the cell growth. Notably, silica NPs do not pass through the Caco-2 cell monolayer after 4-h contact, indicating the low potential of silica NPs to cross the gastrointestinal tract in vivo. Our findings indicate that silica NPs could be used as a safe food additive, but more investigations, such as long-term in vivo exposure, are necessary in future studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of the toxicity of food additive silica nanoparticles on gastrointestinal cells

Yang

Zhang

Cheng

et al. 2013

J of Applied Toxicology

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“…Previous studies have also noted that silica with primary particle size of 32 and 83 nm were taken up by Caco-2 cells, formed larger agglomerates (200 -300 nm), and even showed up in the nucleus after 72 hour exposure with the smaller particles. 43 Silica nanoparticle (NP) uptake by Caco-2 cells by elemental analysis of the cells has been reported, although surface binding versus internalization is not readily distinguished by this method. 37 Internalization of TiO2 NP in Caco-2 cells has also been reported.…”

Section: Particle Uptake By Cellsmentioning

confidence: 99%

Minimal Intestinal Epithelial Cell Toxicity in Response to Short- and Long-Term Food-Relevant Inorganic Nanoparticle Exposure

McCracken

Zane

Knight

et al. 2013

Chem. Res. Toxicol.

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Toxicity of commercial nanoparticles of titania, silica, and zinc oxides is being investigated in this in vitro study. Particles of these compositions are found in many food items, and thus this study is directed toward particle behavior in simulated digestion media and their interaction with intestinal epithelial cell line C2BBe1, a clone of Caco-2 cells, originally isolated from a human colon cancer. Even though the primary particle size of all three particles was below 50 nm, the particles appeared as aggregates in culture media with a negatively charged surface. In the presence of pepsin (pH 2), the charge on the titania became positive, and silica was almost neutral and aggregated extensively, whereas ZnO dissolved. For silica and titania, treatment with simulated intestinal digestive solution led to a strongly negatively charged surface and particle sizes approaching values similar to those in media. On the basis of infrared spectroscopy, we concluded that the surface of silica and titania was covered with bile salts/proteins after this treatment. Transmission electron microscopy indicated that the C2BBe1 cells internalized all three particles. Toxicity assays included investigation of necrosis, apoptosis, membrane damage, and mitochondrial activity. Titania and SiO2 particles suspended in media at loading levels of 10 μg/cm2 exhibited no toxicity. With ZnO at the same loading level, mild toxicity was observed based only on the LDH assay and decrease of mitochondrial activity and not necrosis or apoptosis. Titania particles exposed to the simulated digestion media exhibited mild toxicity based on decrease of mitochondrial activity, likely due to transport of toxic bile salts via adsorption on the particle surface.

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“…Of these characteristics, the particle size is a crucial factor which determines NP endocytosis pathway [17,18], uptake rate and efficiency [6,16,[19][20][21][22], in vitro cytotoxicity [23][24][25][26][27][28], immune responses [27][28][29][30], and the final localisation [15,31,32]. Thus size-dependent uptake of various NPs has been intensively investigated and widely reported.…”

Section: Introductionmentioning

confidence: 99%

Particle size- and number-dependent delivery to cells by layered double hydroxide nanoparticles

Dong

Parekh

2015

Journal of Colloid and Interface Science

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a b s t r a c tIt is well known that delivery efficiency to cells is highly dependent on particle size and the administered dose. However, there is a marked discrepancy in many reports, mainly due to the inconsistency in assessment of various parameters. In this particular research, we designed experiments using layered double hydroxide nanoparticles (LDH NPs) to specifically elucidate the effect of particle size, dose and dye loading manner on cellular uptake. Using the number of LDH NPs taken up by HCT-116 cells as the indicator of delivery efficiency, we found that (1) the size of sheet-like LDH in the range of 40-100 nm did not significantly affect their cellular uptake; (2) cellular uptake of 40 and 100 nm LDH NPs was increased proportionally to the number concentration below a critical value, but remained relatively constant beyond the critical value; and (3) the effect of the dye loading manner is mainly dependent on the loading capacity or yield. In particular, the loading capacity is determined by the NP specific surface area. This research may be extended to a larger size range to examine the size effect, but suggests that it is necessary to set up a protocol to evaluate the effects of NP's physicochemical properties on the cellular delivery efficiency.

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Size-Dependent Localization and Quantitative Evaluation of the Intracellular Migration of Silica Nanoparticles in Caco-2 Cells

Cited by 50 publications

References 61 publications

Evaluation of the toxicity of food additive silica nanoparticles on gastrointestinal cells

Evaluation of the toxicity of food additive silica nanoparticles on gastrointestinal cells

Minimal Intestinal Epithelial Cell Toxicity in Response to Short- and Long-Term Food-Relevant Inorganic Nanoparticle Exposure

Particle size- and number-dependent delivery to cells by layered double hydroxide nanoparticles

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