title: Alginate-Iron Speciation and Its Effect on In Vitro Cellular Iron Metabolism.
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.
authors.affiliation: University of Birmingham, School of Cancer Sciences, College of Medical and Dental Sciences, Vincent Drive, Edgbaston, Birmingham, B15 2TT, United Kingdom.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Horniblow
authors.affiliation: University of Birmingham, School of Physics, College of Engineering and Physical Sciences, Edgbaston, Birmingham, B15 2TT, United Kingdom.
authors.forename: Miriam
authors.initials: M
authors.lastname: Dowle
authors.affiliation: University of Birmingham, School of Cancer Sciences, College of Medical and Dental Sciences, Vincent Drive, Edgbaston, Birmingham, B15 2TT, United Kingdom.
authors.forename: Tariq H
authors.initials: TH
authors.lastname: Iqbal
authors.affiliation: Diabetes and Nutritional Sciences, King's College London, Franklin Wilkins Building, 150 Stamford Street, London, SE1 9NH, United Kingdom.
authors.forename: Gladys O
authors.initials: GO
authors.lastname: Latunde-Dada
authors.affiliation: University of Birmingham, School of Physics, College of Engineering and Physical Sciences, Edgbaston, Birmingham, B15 2TT, United Kingdom.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Palmer
authors.affiliation: University of Birmingham, School of Chemistry, College of Engineering and Physical Sciences, Edgbaston, Birmingham, B15 2TT, United Kingdom.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Pikramenou
authors.affiliation: University of Birmingham, School of Cancer Sciences, College of Medical and Dental Sciences, Vincent Drive, Edgbaston, Birmingham, B15 2TT, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Tselepis
mesh_terms: D000464:Alginates / Q000737:chemistry*; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry*; D006801:Humans; D017136:Ion Transport / Q000502:physiology*; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D058085:Iron Compounds / Q000737:chemistry*; D018613:Microscopy, Confocal; D017348:Microscopy, Electron, Scanning Transmission; D053758:Nanoparticles / Q000737:chemistry
chemical_list: D000464:Alginates; D002614:Chelating Agents; D058085:Iron Compounds; D007501:Iron