Impact of food components during in vitro digestion of silver nanoparticles on cellular uptake and cytotoxicity in intestinal cells

Abstract

Because of the rising application of nanoparticles in food and food-related products, we investigated the influence of the digestion process on the toxicity and cellular uptake of silver nanoparticles for intestinal cells. The main food components--carbohydrates, proteins and fatty acids--were implemented in an in vitro digestion process to simulate realistic conditions. Digested and undigested silver nanoparticle suspensions were used for uptake studies in the well-established Caco-2 model. Small-angle X-ray scattering was used to estimate particle core size, size distribution and stability in cell culture medium. Particles proved to be stable and showed radii from 3.6 to 16.0 nm. Undigested particles and particles digested in the presence of food components were comparably taken up by Caco-2 cells, whereas the uptake of particles digested without food components was decreased by 60%. Overall, these findings suggest that in vivo ingested poly (acrylic acid)-coated silver nanoparticles may reach the intestine in a nanoscaled form even if enclosed in a food matrix. While appropriate for studies on the uptake into intestinal cells, the Caco-2 model might be less suited for translocation studies. Moreover, we show that nanoparticle digestion protocols lacking food components may lead to misinterpretation of uptake studies and inconclusive results.

Is nano safe in foods? Establishing the factors impacting the gastrointestinal fate and toxicity of organic and inorganic food-grade nanoparticles

“…123 Another in vitro study showed that the presence of a digested food matrix enhanced the absorption of silver nanoparticles by intestinal epithelium cells. 124 These findings demonstrated that the characteristics of the nanoparticles inside the GIT may be appreciably different to those of the original (pristine) nanoparticles, which is often ignored in biological fate and toxicity assessments of food nanoparticles potentially leading to unrealistic and misleading results.…”

“…12,34 The effects of the food matrix on the behavior of silver nanoparticles are ignored in cell culture studies, but one recent study showed that certain food components did have an appreciable impact on the absorption and toxicity of silver nanoparticles in intestinal cells. 35 A common issue with cell culture studies is that the dose of nanoparticles used is much higher than would ever be found in practice, and is therefore not physiologically relevant.…”

Prediction of Oral Absorption of Nanoparticles from Biorelevant Matrices Using a Combination of Physiologically Relevant In Vitro and Ex Vivo Models

“…To date, only a limited number of studies have included an in vitro digestion step of the NPs prior to determining their permeability across different cell systems (e.g. Lichtenstein et al [21], Walczak et al [22]). In these studies, the in vitro digestion matrix is diluted before being applied on the cell systems to prevent cytotoxicity already to the digestion matrix used.…”

Nanomaterialien in Lebensmitteln – toxikologische Eigenschaften und Risikobewertung

“…Stattdessen kommen zum Studium dieser Phänomene zumeist artifizielle Modelle des Verdauungstrakts zur Anwendung, welche die verschiedenen Abschnitte der gastrointestinalen Passage und ihre chemischen Gegebenheiten, wie etwa den Speichel in der Mundhöhle, den Magensaft oder die intestinale Flüs-sigkeit, nachstellen. Dies ermöglicht eine Untersuchung der Partikeleigenschaften entlang der Teilschritte der Verdauung auch unter der Berücksichtigung der gleichzeitigen Präsenz verschiedener Nahrungsmittelbestandteile [27,28,30,32,33]. In diesem Zusammenhang wird diskutiert und untersucht, inwieweit Nanopartikel aufgrund ihrer geringen Grö-ße möglicherweise bevorzugt physiologische Barrieren überwinden und somit in Zellen oder Gewebe aufgenommen werden können.…”