Abstract
FDA has approved iron oxide nanoparticles (IONs) coated with organic compounds as a safe material with less toxic effects compared with the naked metal ions and nanoparticles. In this study, the biological and physicochemical characteristics of a nanostructured iron-polysaccharide complexes (Nano-IPC) biosynthesized by Enterobacter sp. were evaluated. Furthermore, the serum biochemical parameters, tissue iron level, red blood cell parameters, and organ ferritin of rats were measured for investigating the effect of the Nano-IPCs in comparison with FeSO4 as a supplement for iron deficiency. The biosafety data demonstrated 35% increment of viability in Hep-G2 hepatocarcinoma cell lines when treated with nanoparticles (500 μg/mL) for 24 h. Besides, iron concentration in serum and tissue as well as the expression of ferritin L subunit in animals treated with the Nano-IPCs supplement were meaningfully higher than the FeSO4-supplemented and negative control animals. Moreover, the expression level of ferritin H subunit and biochemical factors remained similar to the negative control animals in the Nano-IPC-supplemented group. These results indicated that Nano-IPCs can be considered as a nontoxic supplement for patients carrying iron-deficiency anemia (IDA).
Similar content being viewed by others
References
Vasantharaj S, Sathiyavimal S, Senthilkumar P, LewisOscar F, Pugazhendhi A (2019) Biosynthesis of iron oxide nanoparticles using leaf extract of Ruellia tuberosa: antimicrobial properties and their applications in photocatalytic degradation. J Photochem Photobiol B 192:74–82
Pugazhendhi A, Prabhu R, Muruganantham K, Shanmuganathan R, Natarajan S (2019) Anticancer, antimicrobial and photocatalytic activities of green synthesized magnesium oxide nanoparticles (MgONPs) using aqueous extract of Sargassum wightii. J Photochem Photobiol 190:86–97
Saravanan M, Arokiyaraj S, Lakshmi T, Pugazhendhi A (2019) Synthesis of silver nanoparticles from Phenerochaete chrysosporium (MTCC-787) and their antibacterial activity against human pathogenic bacteria. Microb Pathog 117:68–72
He Y, Du Z, Lv H, Jia Q, Tang Z, Zheng X, Zhang K, Zhao F (2013) Green synthesis of silver nanoparticles by Chrysanthemum morifolium Ramat. Extract and their application in clinical ultrasound gel. Int J Nanomedicine 8:1809–1815
Baldi F, Minacci A, Pepi M, Scozzafava A (2001) Gel sequestration of heavy metals by Klebsiella oxytoca isolated from iron mat. FEMS Microbiol Ecol 36:169–174
Iravani S (2014) Bacteria in nanoparticle synthesis: current status and future prospects. Int Scholarly Res 2014:1–18
Wang P-t, Song Y-h, Fan H-c, Yu L (2018) Bioreduction of azo dyes was enhanced by in-situ biogenic palladium nanoparticles. Bioresour Technol 266:176–180
Ghanbariasad A, Taghizadeh S-M, Show PL, Nomanbhay S, Berenjian A, Ghasemi Y, Ebrahiminezhad A (2019) Controlled synthesis of iron oxyhydroxide (FeOOH) nanoparticles using secretory compounds from Chlorella vulgaris microalgae. Bioengineered 10:390–396
Casentini B, Gallo M, Baldi F (2019) Arsenate and arsenite removal from contaminated water by iron oxides nanoparticles formed inside a bacterial exopolysaccharide. J Environ Chem Eng 7:102908
Ahmad A, Senapati S, Khan MI, Kumar R, Sastry M (2003) Extracellular biosynthesis of monodisperse gold nanoparticles by a novel extremophilic actinomycete, Thermomonospora sp. Langmuir 19:3550–3553
Kianpour S, Ebrahiminezhad A, Mohkam M, Tamaddon AM, Dehshahri A, Heidari R, Ghasemi Y (2017) Physicochemical and biological characteristics of the nanostructured polysaccharide-iron hydrogel produced by microorganism Klebsiella oxytoca. J Basic Microbiol 57:132–140
Picceri GG, Leonardi P, Iotti M, Gallo M, Baldi F, Zambonelli A, Amicucci A, Vallorani L, Piccoli G, Ciccimarra G, Arshakyan M, Burattini S, Falcieri E, Chiarantini L (2018) Bacteria-produced ferric exopolysaccharide nanoparticles as iron delivery system for truffles (tuber borchii). Appl Microbiol Biotechnol 102:1429–1441
Ebrahiminezhad A, Zare M, Kiyanpour S, Berenjian A, Niknezhad SV, Ghasemi Y (2017) Biosynthesis of xanthan gum coated iron nanoparticles by using Xanthomonas campestris. IET Nanobiotechnol 12:254–258
Shafie EH, Keshavarz SA, Kefayati ME, Taheri F, Sarbakhsh P, Vafa MR (2016) The effects of nanoparticles containing iron on blood and inflammatory markers in comparison to ferrous sulfate in anemic rats. Int J Prev Med. https://doi.org/10.4103/2008-7802.193092
Low M, Farrell A, Biggs B-A, Pasricha S-R (2013) Effects of daily iron supplementation in primary-school–aged children: systematic review and meta-analysis of randomized controlled trials. CMAJ 185:791–802
Sadighi J, Mohammad K, Sheikholeslam R, Torabi P, Salehi F, Abdolahi Z, Pouraram H (2010) Flour fortification with iron and folic acid in Bushehr and Golestan provinces, Iran: program evaluation. J School Public Health Inst Public Health Res 7:11–24
Cancelo-Hidalgo MJ, Castelo-Branco C, Palacios S, Haya-Palazuelos J, Ciria-Recasens M, Manasanch J, Pérez-Edo L (2013) Tolerability of different oral iron supplements: a systematic review. Curr Med Res Opin 29:291–303
Coe EM, Bowen LH, Speer JA, Bereman RD (1995) Comparison of polysaccharide iron complexes used as iron supplements. J Inorg Biochem 57:287–292
Mahler GJ, Esch MB, Tako E, Southard TL, Archer SD, Glahn RP, Shuler ML (2012) Oral exposure to polystyrene nanoparticles affects iron absorption. Nat Nanotechnol 7:264
Jani P, Halbert GW, Langridge J, Florence AT (1990) Nanoparticle uptake by the rat gastrointestinal mucosa: quantitation and particle size dependency. J Pharm Pharmacol 42:821–826
Bergin IL, Witzmann FA (2013) Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gaps. J Biomed Nanosci Nanotechnol 3:163–210
Mohie-Eldin MY, Frankel RB, Gunther L (1994) A comparison of the magnetic properties of polysaccharide iron complex (PIC) and ferritin. J Magn Magn Mater 135:65–81
Wolfe R, Thauer R, Pfennig N (1987) A ‘capillary racetrack’method for isolation of magnetotactic bacteria. FEMS Microbiol Ecol 3:31–35
Lovley DR, Giovannoni SJ, White DC, Champine JE, Phillips EJP, Gorby YA, Goodwin S (1993) Geobacter metallireducens gen. nov. sp. nov., a microorganism capable of coupling the complete oxidation of organic compounds to the reduction of iron and other metals. Arch Microbiol 159:336–344
Kazemi A, Mousavi-Khorshidi S, Ghoshoon M, Raee M (2010) Halotoleraiit amylase production by a novel bacterial strain, Rheinheimera aquimaris. Res J Microbiol 5:144–149
Farzan F, Shojaosadati SA, Abdul Tehrani H (2010) A preliminary report on the isolation and identification of Magnetotactic bacteria from Iran environment. Iran J Biotechnol 8:98–102
Klaus T, Joerger R, Olsson E, Granqvist C-G (1999) Silver-based crystalline nanoparticles, microbially fabricated. Proc Natl Acad Sci U S A 96:13611
Sinha A, Khare SK (2011) Mercury bioaccumulation and simultaneous nanoparticle synthesis by Enterobacter sp. cells. Bioresour Technol 102:4281–4284
Baldi F, Marchetto D, Paganelli S, Piccolo O (2011) Bio-generated metal binding polysaccharides as catalysts for synthetic applications and organic pollutant transformations. New Biotechnol 29:74–78
Ge Y, Zhang Y, He S, Nie F, Teng G, Gu N (2009) Fluorescence modified chitosan-coated magnetic nanoparticles for high-efficient cellular imaging. Nanoscale Res Lett 4:287–295
Gholami A, Rasoul-amini S, Ebrahiminezhad A, Seradj SH, Ghasemi Y (2015) Lipoamino acid coated Superparamagnetic Iron oxide nanoparticles concentration and time dependently enhanced growth of human Hepatocarcinoma cell line (Hep-G2). J Nanomater. https://doi.org/10.1155/2015/451405
Arčon I, Piccolo O, Paganelli S, Baldi F (2012) XAS analysis of a nanostructured iron polysaccharide produced anaerobically by a strain of Klebsiella oxytoca. Biometals 25:875–881
Santra S, Tapec R, Theodoropoulou N, Dobson J, Hebard A, Tan W (2001) Synthesis and characterization of silica-coated iron oxide nanoparticles in microemulsion: the effect of nonionic surfactants. Langmuir 17:2900–2906
Anilreddy B (2009) Preparation and characterization of Iron oxide nanoparticles on disaccharide templates. JPRHC 1:172–183
Meléndrez MF, Cárdenas G, Arbiol J (2010) Synthesis and characterization of gallium colloidal nanoparticles. J Colloid Interface Sci 346:279–287
Mohammadpour Dounighi N, Mehrabi M, Avadi M, Zolfagharian H, Rezayat M (2016) Preparation, characterization and stability investigation of chitosan nanoparticles loaded with the Echis carinatus snake venom as a novel delivery system. Arch Razi Inst 70:269–277
Singh A, Sahoo SK (2014) Magnetic nanoparticles: a novel platform for cancer theranostics. Drug Discov Today 19:474–481
Naqvi S, Samim M, Abdin M, Ahmed FJ, Maitra A, Prashant C, Dinda AK (2009) Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress. Int J Nanomedicine 5:983–989
Mahmoudi M, Simchi A, Imani M, Shokrgozar MA, Milani AS, Häfeli UO, Stroeve P (2010) A new approach for the in vitro identification of the cytotoxicity of superparamagnetic iron oxide nanoparticles. Colloid Surf 75:300–309
Peña-Rosas JP, De-Regil LM, Dowswell T, Viteri FE (2012) Daily oral iron supplementation during pregnancy. Cochrane Libr. https://doi.org/10.1002/14651858.CD004736
Xiao C, Lei X, Wang Q, Du Z, Jiang L, Chen S, Zhang M, Zhang H, Ren F (2016) Effects of a tripeptide iron on iron-deficiency anemia in rats. Biol Trace Elem Res 169:211–217
Brugnara C, Zelmanovic D, Sorette M, Ballas SK, Platt O (1997) Reticulocyte hemoglobin: an integrated parameter for evaluation of erythropoietic activity. Am J Clin Pathol 108:133–142
Pereira DI, Bruggraber SF, Faria N, Poots LK, Tagmount MA, Aslam MF, Frazer DM, Vulpe CD, Anderson GJ, Powell JJ (2014) Nanoparticulate iron (III) oxo-hydroxide delivers safe iron that is well absorbed and utilised in humans. Nanomed-Nanotechnol 10:1877–1886
Lomer MC, Cook WB, Jan-Mohamed HJB, Hutchinson C, Liu DY, Hider RC, Powell JJ (2012) Iron requirements based upon iron absorption tests are poorly predicted by haematological indices in patients with inactive inflammatory bowel disease. Brit J Nutr 107:1806–1811
Schümann K, Solomons NW, Romero-Abal M-E, Orozco M, Weiss G, Marx J (2012) Oral administration of ferrous sulfate, but not of iron polymaltose or sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), results in a substantial increase of non-transferrin-bound iron in healthy iron-adequate men. Food Nutr Bull 33:128–136
Mattix B, Olsen TR, Moore T, Casco M, Simionescu D, Visconti RP, Alexis F (2014) Accelerated iron oxide nanoparticle degradation mediated by polyester encapsulation within cellular spheroids. Adv Funct Mater 24:800–807
Chorny M, Alferiev IS, Fishbein I, Tengood JE, Folchman-Wagner Z, Forbes SP, Levy RJ (2012) Formulation and in vitro characterization of composite biodegradable magnetic nanoparticles for magnetically guided cell delivery. Pharm Res 29:1232–1241
Jacobs A, Miller F, Worwood M, Beamish M, Wardrop C (1972) Ferritin in the serum of normal subjects and patients with iron deficiency and iron overload. Br Med J 4:206–208
Lipschitz D, Cook J, Finch C (1992) A clinical evaluation of serum ferritin as an index of iron stores. Nutrition 8:443–447
Nakanishi T, Kuragano T, Nanami M, Otaki Y, Nonoguchi H, Hasuike Y (2010) Importance of ferritin for optimizing anemia therapy in chronic kidney disease. Am J Nephrol 32:439–446
Harrison PM, Arosio P (1996) The ferritins: molecular properties, iron storage function and cellular regulation. BBA-Bioenergetics 1275:161–203
Fahmy M, Young SP (1993) Modulation of iron metabolism in monocyte cell line U937 by inflammatory cytokines: changes in transferrin uptake, iron handling and ferritin mRNA. Biochem J 296:175–181
Tsuji Y, Ayaki H, Whitman SP, Morrow CS, Torti SV, Torti FM (2000) Coordinate transcriptional and translational regulation of ferritin in response to oxidative stress. Mol Cell Biol 20:5818–5827
Muckenthaler M, Richter A, Gunkel N, Riedel D, Polycarpou-Schwarz M, Hentze S, Falkenhahn M, Stremmel W, Ansorge W, Hentze MW (2003) Relationships and distinctions in iron-regulatory networks responding to interrelated signals. Blood 101:3690–3698
Leggett B, Fletcher L, Ramm G, Powell L, Halliday J (1993) Differential regulation of ferritin H and L subunit mRNA during inflammation and long-term iron overload. J Gastroenterol Hepatol 8:21–27
Cairo G, Bardella L, Schiaffonati L, Arosio P, Levi S, Bernelli-Zazzera A (1985) Multiple mechanisms of iron-induced ferritin synthesis in HeLa cells. Biochem Biophys Res Commun 133:314–321
Zariwala MG, Elsaid N, Jackson TL, López FC, Farnaud S, Somavarapu S, Renshaw D (2013) A novel approach to oral iron delivery using ferrous sulphate loaded solid lipid nanoparticles. Int J Pharm 456:400–407
Muntané-Relat J, Ourlin J-C, Domergue J, Maurel P (1995) Differential effects of cytokines on the inducible expression of CYP1A1, CYP1A2, and CYP3A4 in human hepatocytes in primary culture. Hepatology 22:1143–1153
Vanarsa K, Ye Y, Han J, Xie C, Mohan C, Wu T (2012) Inflammation associated anemia and ferritin as disease markers in SLE. Arthritis Res Ther 14:1–9. https://doi.org/10.1186/ar4012
Dobrovolskaia MA, Vogel SN (2002) Toll receptors, CD14, and macrophage activation and deactivation by LPS. Microbes Infect 4:903–914
Kumagai T, Awai M, Okada S (1992) Mobilization of iron and iron-related proteins in rat spleen after intravenous injection of lipopolysaccharides (LPS). Pathol Res Pract 188:931–941
Cobben N, Drent M, Schols A, Lamers R, Wouters E, Van Dieijen-Visser M (1997) Serum lactate dehydrogenase and its isoenzyme pattern in ex-coalminers. Respir Med 91:616–623
Bansal S, Kaw J (1981) Lactate dehydrogenase isoenzymes in macrophages and serum during the development of pulmonary silicosis in the rat. Toxicol Lett 7:279–283
Toblli JE, Cao G, Oliveri L, Angerosa M (2013) Effects of iron polymaltose complex, ferrous fumarate and ferrous sulfate treatments in anemic pregnant rats, their fetuses and placentas. Inflamm Allergy Drug Targets 12:190–198
Acknowledgments
This research is based on the Postdoc research proposal No. 18521 submitted to School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. A Grant from the Research Council of Shiraz University of Medical Sciences supported it.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declared that they have no conflict of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic Supplementary Material
Rights and permissions
About this article
Cite this article
Kianpour, S., Ebrahiminezhad, A., Heidari, R. et al. Enterobacter sp. Mediated Synthesis of Biocompatible Nanostructured Iron-Polysaccharide Complexes: a Nutritional Supplement for Iron-Deficiency Anemia. Biol Trace Elem Res 198, 744–755 (2020). https://doi.org/10.1007/s12011-020-02101-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12011-020-02101-2