The Nano–Intestine Interaction: Understanding the Location‐Oriented Effects of Engineered Nanomaterials in the Intestine

Cui, Xuejing; Bao, Lin; Wang, Xiaoyu; Chen, Chunying

doi:10.1002/smll.201907665

Cited by 45 publications

(33 citation statements)

References 146 publications

(162 reference statements)

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“…Oral method of administration brings the NPs in immediate contact with the gastrointestinal tract. It is possible that NPs: (i) are accumulated in the mucous layer and either get quickly removed from the organism with the mucous layer renewal, or penetrate the deeper layers of the intestinal wall, remaining in the organism much longer; (ii) display their bactericidal properties by affecting the intestinal microbiota; (iii) interact with the intestinal epithelial cells causing local inflammation, (iv) penetrate the intestinal lymphatic tissue affecting the intestinal immunity; and (v) through the intestinal epithelium reach the bloodstream and affect other organs, the liver in particular [ 74 ]. The mechanisms of further AgNPs action in the organism depend on the type of interaction between the nanoparticles and the gastrointestinal tract.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Study of Entero- and Hepatotoxicity of Silver Nanoparticles Stabilized with Benzyldimethyl-[3-myristoylamine)-propyl]ammonium Chloride (Miramistin) to CBF1 Mice upon Enteral Administration

et al. 2021

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Silver nanoparticles (AgNPs) are the most widely studied antimicrobial nanomaterials. However, their use in biomedicine is currently limited due to the availability of data that prove the nanosilver toxicity associated primarily with oxidative stress development in mammalian cells. The surface modification of AgNPs is a potent technique of improvement of their biocompatibility. The synthetic or natural compounds that combine zero or low toxicity towards human and animal organisms with inherent antimicrobial properties are the most promising stabilizing agents, their use would also minimize the risks of microorganisms developing resistance to silver-based materials. We used a simple technique to obtain 30–60 nm AgNPs stabilized with benzyldimethyl[3-myristoylamine)-propyl]ammonium chloride monohydrate (BAC)—a well-known active ingredient of many antibacterial drugs. The objective of the study was to assess the AgNPs-BAC entero- and hepatotoxicity to CBF1 mice upon enteral administration. The animals were exposed to 0.8–7.5 mg/kg doses of AgNPs-BAC in the acute and to 0.05–2.25 mg/kg doses of AgNPs-BAC in the subacute experiments. No significant entero- and hepatotoxic effects following a single exposure to doses smaller than 4 mg/kg were detected. Repeated exposure to the doses of AgNPs-BAC below 0.45 mg/kg and to the doses of BAC below 0.5 mg/kg upon enteral administration also led to no adverse effects. During the acute experiment, the higher AgNPs-BAC dose resulted in increased quantities of aminotransferases and urea, as well as the albumin-globulin ratio shift, which are indicative of inflammatory processes. Besides, the relative mass of the liver of mice was smaller compared to the control. During the subacute experiment, the groups treated with the 0.25–2.25 mg/kg dose of AgNPs-BAC had a lower weight gain rate compared to the control, while the groups treated with the 2.25 mg/kg dose of AgNPs-BAC showed statistically significant variations in the blood serum transaminases activity, which indicated hepatosis. It should be noted that the spleen and liver of the animals from the groups treated with the 0.45 and 2.25 mg/kg dose of AgNPs-BAC were more than two times smaller compared to the control. In the intestines of some animals from the group treated with the 2.25 mg/kg dose of AgNPs-BAC small areas of hyperemia and enlarged Peyer’s patches were observed. Histological examination confirmed the initial stages of the liver and intestinal wall inflammation.

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Section: Discussionmentioning

confidence: 99%

In Vivo Study of Entero- and Hepatotoxicity of Silver Nanoparticles Stabilized with Benzyldimethyl-[3-myristoylamine)-propyl]ammonium Chloride (Miramistin) to CBF1 Mice upon Enteral Administration

et al. 2021

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“…Previous studies have shown that NPs with a hydrodynamic diameter of smaller than 5.5 nm can rapidly renal clearance [192], and large NPs are absorbed by mononuclear phagocytic system (MPS) of the liver, causing potential hepatotoxicity [193]. The NPs accumulated in the brain may not be excreted for 4 months [194]. The interaction of NPs with brain directly affects CNS homeostasis, or the interaction between NPs and gut microbiota indirectly affects CNS function via the gut-brain axis [194].…”

Section: Conclusion and Prospectivementioning

confidence: 99%

“…The NPs accumulated in the brain may not be excreted for 4 months [194]. The interaction of NPs with brain directly affects CNS homeostasis, or the interaction between NPs and gut microbiota indirectly affects CNS function via the gut-brain axis [194]. Therefore, as an ideal nanomedicine, both long-term and short-term toxicity experiments should be investigated, aiming to achieve maximum therapeutic effects and minimize toxic effects.…”

Section: Conclusion and Prospectivementioning

confidence: 99%

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Redox-active nanoparticles for inflammatory bowel disease

2021

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Homeostasis of gut microbiota is extremely essential for maintaining nutrient metabolism and regulating immunological function. The increasing evidence suggests that inflammatory bowel disease (IBD) is strongly associated with dysregulation of gut microbiota. During activated inflammation, excessive reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by inflammatory cells play a detrimental role in regulating IBD and gut microbiota. ROS/RNS cause damage to the surrounding tissues, including nutrient absorption disorders, intestinal dysmotility and barrier dysfunction. Meanwhile, ROS/RNS provide terminal electron receptors for anaerobic respiration and support the bloom of facultative anaerobes, eventually causing gut microbiota dysbiosis. Redox-active nanoparticles (NPs) with catalytic properties or enzyme-like activities can effectively scavenge ROS/RNS, and selectively target inflamed sites via ultrasmall size-mediated enhanced permeation and retention (EPR) effect, showing great potential to regulate IBD and maintain the homeostasis of gut microbiota. In addition, the widespread application of NPs in commercial products has increased their accumulation in healthy organisms, and the biological effects on normal microbiota resulting from long-term exposure of NPs to gastrointestinal tract also need attention.

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“…Hence, humans are increasingly orally exposed to ENM, which has raised safety concerns [13,14]. In the context of ENM safety evaluation, many authors highlighted the importance to account for the intestinal mucus barrier [15][16][17][18]. On the one hand, the interaction of mucus with ENM, such as the entrapping and the formation of a corona, have been extensively researched both in vitro and in vivo [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Ingested Engineered Nanomaterials Affect the Expression of Mucin Genes—An In Vitro-In Vivo Comparison

et al. 2021

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The increasing use of engineered nanomaterials (ENM) in food has fueled the development of intestinal in vitro models for toxicity testing. However, ENM effects on intestinal mucus have barely been addressed, although its crucial role for intestinal health is evident. We investigated the effects of ENM on mucin expression and aimed to evaluate the suitability of four in vitro models of increasing complexity compared to a mouse model exposed through feed pellets. We assessed the gene expression of the mucins MUC1, MUC2, MUC5AC, MUC13 and MUC20 and the chemokine interleukin-8 in pre-confluent and confluent HT29-MTX-E12 cells, in stable and inflamed triple cultures of Caco-2, HT29-MTX-E12 and THP-1 cells, and in the ileum of mice following exposure to TiO2, Ag, CeO2 or SiO2. All ENM had shared and specific effects. CeO2 downregulated MUC1 in confluent E12 cells and in mice. Ag induced downregulation of Muc2 in mice. Overall, the in vivo data were consistent with the findings in the stable triple cultures and the confluent HT29-MTX-E12 cells but not in pre-confluent cells, indicating the higher relevance of advanced models for hazard assessment. The effects on MUC1 and MUC2 suggest that specific ENM may lead to an elevated susceptibility towards intestinal infections and inflammations.

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The Nano–Intestine Interaction: Understanding the Location‐Oriented Effects of Engineered Nanomaterials in the Intestine

Cited by 45 publications

References 146 publications

In Vivo Study of Entero- and Hepatotoxicity of Silver Nanoparticles Stabilized with Benzyldimethyl-[3-myristoylamine)-propyl]ammonium Chloride (Miramistin) to CBF1 Mice upon Enteral Administration

In Vivo Study of Entero- and Hepatotoxicity of Silver Nanoparticles Stabilized with Benzyldimethyl-[3-myristoylamine)-propyl]ammonium Chloride (Miramistin) to CBF1 Mice upon Enteral Administration

Redox-active nanoparticles for inflammatory bowel disease

Ingested Engineered Nanomaterials Affect the Expression of Mucin Genes—An In Vitro-In Vivo Comparison

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