Structure of nanoparticle supplements ‘ironed out’ to improve therapies

The protein haemoglobin works inside red blood cells

Nimrod allows scientists, for the first time, to look at the atomic interactions in iron supplements.
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We might not be coated in an iron exoskeleton, but much like the fictional character Iron Man, this element plays a vital role in powering our bodies. Inside red blood cells, the protein haemoglobin needs iron to be able to capture the oxygen we breathe and deliver it to our tissues. But 20% of the world’s population – about two billion people - are iron deficient, which is one of the leading causes of anaemia. Now scientists are using ISIS’ Nimrod instrument to investigate the molecular structure of the supplements that are used to treat iron deficiency anaemia, with the aim of developing better treatments.

How to treat the most common nutritional disorder in the world?

Iron deficiency is the most common and widespread nutritional disorder in the world and it is the only nutrient deficiency that is significantly prevalent in both industrialised and developing countries.

Treatment usually takes the form of iron supplements; however the supplements often have unpleasant side effects and this leads to problems with patient compliance. Intravenous iron treatment is used in the most serious cases of deficiency or when people have comorbidities such as kidney disease, although this also has potential risks and side effects.

Understanding the iron supplements’ structure and how they behave in the body will be a crucial step in the development of new and improved treatments, with fewer side effects.

Alpha subunit of haemoglobin.

Alpha subunit of haemoglobin. AnnaTanczos, Wellcome Image Library, London. Licensed under Creative Commons Attribution only licence CC BY 4.0
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Nimrod allows scientists, for the first time, to look at the atomic interactions in iron supplements

The Biomineral Research group at the Medical Research Council (MRC) Human Nutrition Research unit (HNR) have been using the Nimrod instrument at ISIS to study clinically important nanoparticles of iron oxides to try to understand more about their atomic structures.

Dr Helen Chappell, of MRC HNR, explains: “We are looking at new compounds produced in our laboratory and comparing their structures to some iron therapeutics that are already in use. We want to understand the relationship between the particles’ structures and their ability to release their iron cargo to cells. Critically, the nanoparticles must remain stable until the body can access the iron safely, which is why structure is so important. More widely, iron nanoparticles have other medical uses apart from treating iron deficiency anaemia, for example in MRI, drug delivery, cell tracking and cancer therapy.”

Both oral and intravenous iron therapies usually have a nanoparticle sized mineral iron core composed of iron oxide, with carbohydrates or other organic molecules bound to it that determine the particle’s solubility and stability. The interaction between these organic coating molecules and the inorganic mineral core is likely to be fundamental in explaining the behaviour of these particles in the body. “These structures are fundamentally difficult to understand,” commented Helen. “For example, the structure of ferrihydrite, a form of which is found in the body’s own iron stores, has an irregular structure that is much more disordered and full of defects than a typical crystal. Consequently, it doesn’t respond well to traditional structural analysis, such as X-ray diffraction.”

The team are therefore using neutrons, which give very sensitive structural measurements, to generate high-resolution data and look more closely at the atomic interaction between the different components of the nanoparticles.

“Nimrod allows us to collect data ranging from particle size and shape to details of bond lengths within the core and interactions at the surface. We can look at our particles in solution, dried or with isotopic substitutions, which will give us the maximum opportunity to decipher the structure.”

The team hope that the data from ISIS will help to better understand existing therapeutics and allow scientists to develop new structures with far improved properties to treat iron deficiency anaemia more effectively and with fewer side effects.

Felice Laake & Helen Chappell

Research date: June 2014

Further Information

For further information please contact Dr Helen Chappell

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