Abstract
Alginates are a class of biopolymers with known iron binding properties which are routinely used in the fabrication of iron-oxide nanoparticles. In addition, alginates have been implicated in influencing human iron absorption. However, the synthesis of iron oxide nanoparticles employs non-physiological pH conditions and whether nanoparticle formation in vivo is responsible for influencing cellular iron metabolism is unclear. Thus the aims of this study were to determine how alginate and iron interact at gastric-comparable pH conditions and how this influences iron metabolism. Employing a range of spectroscopic techniques under physiological conditions alginate-iron complexation was confirmed and, in conjunction with aberration corrected scanning transmission electron microscopy, nanoparticles were observed. The results infer a nucleation-type model of iron binding whereby alginate is templating the condensation of iron-hydroxide complexes to form iron oxide centred nanoparticles. The interaction of alginate and iron at a cellular level was found to decrease cellular iron acquisition by 37% (p < 0.05) and in combination with confocal microscopy the alginate inhibits cellular iron transport through extracellular iron chelation with the resulting complexes not internalised. These results infer alginate as being useful in the chelation of excess iron, especially in the context of inflammatory bowel disease and colorectal cancer where excess unabsorbed luminal iron is thought to be a driver of disease.
Highlights
Alginates are a diverse class of biopolymers extracted from brown algae that are composed of 1–4 linked β-D-mannuronic acid (M) and α-L-guluronic acid (G) monomers
Isothermal Titration Calorimetry (ITC) measurements were performed on a VPITC MicroCalorimeter and data was automatically analysed using MicoCal LLC ITC/Origin software package; the binding isotherm was obtained by integrating injections and fitting them to an appropriate binding model
The binding of ferric ions to alginate was further verified using UV-Visible and Circular Dichroism (CD) spectroscopy. (Fig 1B and 1C) Titration of an aqueous solution of Fe(III) to an aqueous solution of sodium alginate LFR5/60 revealed the growth of a band at 280 nm (Fig 1C); confirming iron binding to alginate
Summary
Alginates are a diverse class of biopolymers extracted from brown algae that are composed of 1–4 linked β-D-mannuronic acid (M) and α-L-guluronic acid (G) monomers. The polymers can vary in both chain length and composition which, in conjunction with their ability to interact with divalent metal cations, endows alginates with a wide range of physicochemical properties. The use of alginate as a scaffold for nanoparticle formulation is a well-accepted synthetic strategy, in these reactions the iron-oxide nanoparticles are fabricated using chemical-forcing conditions whereby highly basic conditions are used to form the iron hydroxide.[5,6,7,8] These conditions are considered optimal for the formation of iron oxide nanoparticles, with mean diameters ranging between 9 to 10 nm.[9,10] whether these iron oxide nanoparticles can form spontaneously in the gastrointestinal tract of man and in particular at low pH conditions of the stomach, (the first reasonable site of interaction between iron and alginate consumed in the diet) is unknown
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