Direct targeting of iron absorption in the gut- the future of iron-overload therapy?


In a recent article in Nanomedicine, Yingfang Fan and colleagues proposed a new approach to the treatment of iron overload (3). They used pH-sensitive gelatin nanoparticles for oral delivery of siRNA targeting divalent metal transport 1 (DMT1). They found that they could decrease DMT1 expression in the mouse gut, and consequently absorption of Fe59. This approach, the authors argued, presented advantages over the use of iron chelators, which lack specificity. This is an interesting new angle in the treatment of iron overload, although the authors have yet to test the efficacy of their method in hemochromatosis mice. What is the translational potential of this approach?.  Well, the oral delivery through pH-sensitive nanoparticles appears to ensure specificity for gut DMT1. Indeed the authors reported that their nanoparticles did not affect DMT1 expression in other tissues. 

One pertinent question is the effect of DMT1 blockade on iron levels, and consequently on the HIF-2α/FPN axis that regulates intestinal iron absorption. This is a space to watch………………

Contributed by Prof Samira Lakhal-Littleton, Department of Physiology, Anatomy & Genetics

University of Oxford