Impact of in vitro digested zinc oxide nanoparticles on intestinal model systems

Abstract

Background Zinc oxide nanoparticles (ZnO NP) offer beneficial properties for many applications, especially in the food sector. Consequently, as part of the human food chain, they are taken up orally. The toxicological evaluation of orally ingested ZnO NP is still controversial. In addition, their physicochemical properties can change during digestion, which leads to an altered biological behaviour. Therefore, the aim of our study was to investigate the fate of two different sized ZnO NP (< 50 nm and < 100 nm) during in vitro digestion and their effects on model systems of the intestinal barrier. Differentiated Caco-2 cells were used in mono- and coculture with mucus-producing HT29-MTX cells. The cellular uptake, the impact on the monolayer barrier integrity and cytotoxic effects were investigated after 24 h exposure to 123–614 µM ZnO NP. Results In vitro digested ZnO NP went through a morphological and chemical transformation with about 70% free zinc ions after the intestinal phase. The cellular zinc content increased dose-dependently up to threefold in the monoculture and fourfold in the coculture after treatment with digested ZnO NP. This led to reactive oxygen species but showed no impact on cellular organelles, the metabolic activity, and the mitochondrial membrane potential. Only very small amounts of zinc (< 0.7%) reached the basolateral area, which is due to the unmodified transepithelial electrical resistance, permeability, and cytoskeletal morphology. Conclusions Our results reveal that digested and, therefore, modified ZnO NP interact with cells of an intact intestinal barrier. But this is not associated with serious cell damage.

Engineering siRNA-loaded and RGDfC-targeted selenium nanoparticles for highly efficient silencing of DCBLD2 gene for colorectal cancer treatment

“…Mitochondrial membrane potential (Δψm), an essential for ATP synthase to make ATP, is established by the proton transfer against their concentration gradient driven by the respiratory electron transport chains in the inner mitochondrial membrane [ 40 ]. It has been reported that the loss of Δψm could lead to the release of apoptotic factors, such as cytochrome C, and activate downstream apoptotic pathways [ 41 ]. JC-1, as a lipophilic cationic dye, was selectively capable of entering into mitochondria and reversibly changing its color from red to green when the Δψm decreased.…”

Potential Toxicity of Nanoparticles for the Oral Delivery of Therapeutics

“…Several studies have found negative biological effects, such as increased intestinal inflammation, reduced cell viability, and mitochondrial membrane depolarization, resulting from the treatment with ZnO NPs. However, modified ZnO NPs do not cause significant cell damage [76,77].…”

Critical aspects in dissolution testing of nanomaterials in the oro-gastrointestinal tract: the relevance of juice composition for hazard identification and grouping

“…Such juices have been widely used for NM digestion. 2,8,[18][19][20][21] The "cascade in vitro digestion assay" is acknowledged as the most popular static assay, which simulates the passage of the NF within the OGI tract under fasting conditions through the sequential addition of simulated saliva, stomach and intestine. 2,8,19,[22][23][24] This assay allows the dissolution kinetics of NFs in semi-realistic environments (cascade addition of biomacromolecules and salts simulating the molecular compositions of the digestive juices and drastic changes in pH values and digestive volumes according to human physiology) to be studied.…”