Project

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Gastrointestinal exposure to nanoscale iron compounds in foods: absorptive pathways and potential toxicity

English title Gastrointestinal exposure to nanoscale iron compounds in foods: absorptive pathways and potential toxicity
Applicant Zimmermann Michael Bruce
Number 141610
Funding scheme NRP 64 Opportunities and Risks of Nanomaterials
Research institution Labor für Humanernährung Institut für Lebensmittel, Ernährung und Gesundheit, ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Nutritional Research, Vitaminology
Start/End 01.07.2012 - 30.06.2016
Approved amount 632'095.00
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Keywords (10)

Nanoparticles; Food; Toxicity; Iron; Absorption; Fortification; Nutrition; in-vivo study; Nanotechnology; Cell studies

Lay Summary (English)

Lead
Lay summary
Nanotechnology will likely provide new opportunities for product development in the food and nutrition industry, including delivery of improved health benefits to consumers. One promising application is increased absorption of nutrients that are often deficient in diets by particle size reduction to the nanoscale. However, a major barrier to the use of nanosized compounds in foods and nutritional supplements is limited understanding of their mechanism of absorption as well as their safety in the gastrointestinal tract. Our objectives are to determine the underlying basis of causal relationships between the physical and chemical properties of nanosized iron compounds, their absorptive pathways and their biological impact in the gastrointestinal tract. We focus on iron in this project because iron deficiency is a common nutrient deficiency, nanosized iron is food compatible but well absorbed, and the food industry is looking for more effective iron fortificants for their products. Our research plan is multidisciplinary and involves close collaboration between material sciences, human nutrition and molecular toxicology and is application-oriented. It has three major parts: 1) Establish the relationship between physical properties of nanosized iron compounds suitable for food fortification with standard in vitro molecular markers relevant to nanoparticle toxicity alerts. 2. Determination of the absorptive pathways of nanosized iron in duodenal-specific DMT-1 knock-out mice. 3. Elucidate the in vivo relationship between nanosized iron for food fortification and toxicity pathways in the gastrointestinal tract. We will first establish the relationship between physical properties of extensively characterized nanoiron compounds previously shown useful for food fortification with standard in vitro molecular markers relevant to nanomaterial toxicity alerts using mammalian epithelial cell models relevant to intestinal transport. Along with standard cell models using carcinoma-derived cells, human colon epithelial cells will be used to evaluate cytotoxicity markers in a system that more closely resembles healthy tissue. In the second part of the project we will determine the absorptive pathways of nanosized iron in duodenal-specific DMT-1 knock-out mice. These mice cannot absorb dietary non-heme iron because they lack the duodenal iron transporter (DMT1). Combined with iron stable isotopes to directly measure iron entering the body, we can use this mouse model to determine if absorption of nanosized iron is through the usual pathway of DMT1 or through less desirable alternate pathways that may be unregulated. In the third part, we perform a long-term dose-response study in mice with nanosized dietary iron to elucidate the in-vivo relationship between nanosized iron food fortificants and potential toxicity pathways in the intestinal mucosa and gut-associated lymphatic tissue. We will test the assays developed in the in-vitro studies in part one of this program to assess toxicity in the gastrointestinal tract. These experiments will reconcile in vitro and in vivo parameters and provide further insights into the chemical and physical properties and effects of nanostructured compounds as they pass through the digestive system. There is keen interest among the Swiss food and nutrition industry to evaluate the potential of nanotechnology in new products. The nanoiron compounds evaluated in these studies have been developed within a large KTI project now in its final year; several of the compounds are currently being tested in food and nutrition products by Swiss industry. But safety issues need to be resolved in order for these promising compounds to move into consumer products. Thus, the proposed studies will provide critical data for the Swiss food and nutrition industry, as well as Swiss regulatory bodies. If shown to be safe, nanoiron compounds may prove to be high performance, ‘next generation’ food fortificants and supplements that could give the Swiss food industry a competitive edge, generate benefits for the Swiss economy and improve consumer health.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Collaboration

Group / person Country
Types of collaboration
Vetrinary Pathology University of Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Diabetes & Nutritional Sciences Division, King's College London Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
- Exchange of personnel
Institute of Pharmacology and Toxicology, University Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
- Exchange of personnel
Particle Technology Laboratory, ETH Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Center for Nanotechnology and Nanotoxicology, Harvard University United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
Laboratroy of Physiology and Behaviour, ETH Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Swiss Chemical Society Meeting Poster Iron phosphate nanoparticles do not impair membrane integrity or metabolic activity in intestinal cell lines 11.09.2014 Zurich, Switzerland von Moos Lea;
CLINAM Summit Talk given at a conference Iron phosphate nanoparticle for food applications do not induce direct cytotoxicity in intestinal cell lines 23.06.2014 Basel, Switzerland von Moos Lea;
Nanotox Conference Poster Iron nanoparticles do not induce direct cytotoxicity in intestinal HT29-MTX and HCEC cells AND Novel nanoscale calcium compounds for nutritional application: production and in vitro dissolution 22.04.2014 Antalya, Turkey Posavec Lidija; Hilty-Vancura Florentine; von Moos Lea;
Eurotox Meeting Poster Iron phosphate nanoparticles do not impair membrane integrity or metabolic activity in intestinal cell lines 01.09.2013 Interlaken, Switzerland von Moos Lea;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Seminar Talk 14.01.2014 Lausanne, Switzerland Zimmermann Michael Bruce; Hilty-Vancura Florentine;
Expo Nano Technorama Winterthur Performances, exhibitions (e.g. for education institutions) 08.10.2013 Winterthur , Switzerland Hilty-Vancura Florentine;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Iron phosphate nanoparticle for food applications do not induce direct cytotoxicity German-speaking Switzerland 2014

Awards

Title Year
Educational Award, NANOTOX 2014, 7th International Nanotoxicology Congress, Antalya, Turkey, April 2014. Award is covering attendance and accommodation fees (up to 1000 EUR) for participation on 3-day training course “From Detection to Imaging of ROS and NO in vitro and in vivo using ESR”. Supported by: Noxygen Science Transfer & Diagnostics GmbH and Bruker Biospin GmbH 2014

Associated projects

Number Title Start Funding scheme
186332 Hijacking Transcription-Coupled DNA Repair for Cancer Therapy 01.01.2020 Sinergia
149090 Using novel nano- and pheroid-technologies to enhance calcium delivery for food and nutrition applications: production, characterization and in vivo efficacy 01.01.2014 Bilateral programmes

Abstract

Nanotechnology will likely provide new opportunities for product development in the food and nutrition industry, including delivery of improved health benefits to consumers. One promising application is increased absorption of nutrients that are often deficient in diets by particle size reduction to the nanoscale. However, a major barrier to the use of nanosized compounds in foods and nutritional supplements is limited understanding of their mechanism of absorption as well as their safety in the gastrointestinal tract. Our objectives are to determine the underlying basis of causal relationships between the physical and chemical properties of nanosized iron compounds, their absorptive pathways and their biological impact in the gastrointestinal tract. We focus on iron in this project because iron deficiency is a common nutrient deficiency, nanosized iron is food compatible but well absorbed, and the food industry is looking for more effective iron fortificants for their products. Our research plan is multidisciplinary and involves close collaboration between material sciences, human nutrition and molecular toxicology and is application-oriented. It has three major parts: 1) Establish the relationship between physical properties of nanosized iron compounds suitable for food fortification with standard in vitro molecular markers relevant to nanoparticle toxicity alerts. 2. Determination of the absorptive pathways of nanosized iron in duodenal-specific DMT-1 knock-out mice. 3. Elucidate the in vivo relationship between nanosized iron for food fortification and toxicity pathways in the gastrointestinal tract. We will first establish the relationship between physical properties of extensively characterized nanoiron compounds previously shown useful for food fortification with standard in vitro molecular markers relevant to nanomaterial toxicity alerts using mammalian epithelial cell models relevant to intestinal transport. Along with standard cell models using carcinoma-derived cells, human colon epithelial cells will be used to evaluate cytotoxicity markers in a system that more closely resembles healthy tissue. In the second part of the project we will determine the absorptive pathways of nanosized iron in duodenal-specific DMT-1 knock-out mice. These mice cannot absorb dietary non-heme iron because they lack the duodenal iron transporter (DMT1). Combined with iron stable isotopes to directly measure iron entering the body, we can use this mouse model to determine if absorption of nanosized iron is through the usual pathway of DMT1 or through less desirable alternate pathways that may be unregulated. In the third part, we perform a long-term dose-response study in mice with nanosized dietary iron to elucidate the in-vivo relationship between nanosized iron food fortificants and potential toxicity pathways in the intestinal mucosa and gut-associated lymphatic tissue. We will test the assays developed in the in-vitro studies in part one of this program to assess toxicity in the gastrointestinal tract. These experiments will reconcile in vitro and in vivo parameters and provide further insights into the chemical and physical properties and effects of nanostructured compounds as they pass through the digestive system. There is keen interest among the Swiss food and nutrition industry to evaluate the potential of nanotechnology in new products. The nanoiron compounds evaluated in these studies have been developed within a large KTI project now in its final year; several of the compounds are currently being tested in food and nutrition products by Swiss industry. But safety issues need to be resolved in order for these promising compounds to move into consumer products. Thus, the proposed studies will provide critical data for the Swiss food and nutrition industry, as well as Swiss regulatory bodies. If shown to be safe, nanoiron compounds may prove to be high performance, ‘next generation’ food fortificants and supplements that could give the Swiss food industry a competitive edge, generate benefits for the Swiss economy and improve consumer health.
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