{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:05:30Z","timestamp":1792040730836,"version":"4.4.0"},"reference-count":39,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RO-JINR","award":["Projects No. 365\/11.05.2021, items 8, 87 and 98"],"award-info":[{"award-number":["Projects No. 365\/11.05.2021, items 8, 87 and 98"]}]},{"DOI":"10.13039\/501100003822","name":"Joint Institute for Nuclear Research","doi-asserted-by":"publisher","award":["Projects No. 366\/11.05.2021, items 7, 86 and 97"],"award-info":[{"award-number":["Projects No. 366\/11.05.2021, items 7, 86 and 97"]}],"id":[{"id":"10.13039\/501100003822","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human serum transferrin (HST) is a glycoprotein involved in iron transport that may be a candidate for functionalized nanoparticles to bind and target cancer cells. In this study, the effects of the simple and doped with cobalt (Co) and copper (Cu) ferrihydrite nanoparticles (Fh-NPs, Cu-Fh-NPs, and Co-Fh-NPs) were studied by spectroscopic and molecular approaches. Fluorescence spectroscopy revealed a static quenching mechanism for all three types of Fh-NPs. All Fh-NPs interacted with HST with low affinity, and the binding was driven by hydrogen bonding and van der Waals forces for simple Fh-NPs and by hydrophobic interactions for Cu-Fh-NPs and Co-Fh-NPs binding, respectively. Of all samples, simple Fh-NPs bound the most to the HST binding site. Fluorescence resonance energy transfer (FRET) allowed the efficient determination of the energy transfer between HST and NPs and the distance at which the transfer takes place and confirmed the mechanism of quenching. The denaturation of the HST is an endothermic process, both in the case of apo HST and HST in the presence of the three types of Fh-NPs. Molecular docking studies revealed that Fh binds with a low affinity to HST (Ka = 9.17 \u00d7 103 M\u22121) in accord with the fluorescence results, where the interaction between simple Fh-NPs and HST was described by a binding constant of 9.54 \u00d7 103 M\u22121.<\/jats:p>","DOI":"10.3390\/ijms22137034","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T10:52:46Z","timestamp":1624963966000},"page":"7034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Interactions of Chemically Synthesized Ferrihydrite Nanoparticles with Human Serum Transferrin: Insights from Fluorescence Spectroscopic Studies"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3662-9268","authenticated-orcid":false,"given":"Claudia G.","family":"Chilom","sequence":"first","affiliation":[{"name":"Department of Electricity, Solid Physics and Biophysics, Faculty of Physics, University of Bucharest, Str Atomistilor 405, CP MG 11, RO-077125 M\u0103gurele, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoleta","family":"Sandu","sequence":"additional","affiliation":[{"name":"Department of Electricity, Solid Physics and Biophysics, Faculty of Physics, University of Bucharest, Str Atomistilor 405, CP MG 11, RO-077125 M\u0103gurele, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorina","family":"Iftimie","sequence":"additional","affiliation":[{"name":"Department of Electricity, Solid Physics and Biophysics, Faculty of Physics, University of Bucharest, Str Atomistilor 405, CP MG 11, RO-077125 M\u0103gurele, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0900-2654","authenticated-orcid":false,"given":"Maria","family":"B\u0103l\u0103\u015foiu","sequence":"additional","affiliation":[{"name":"Joint Institute for Nuclear Research, Joliot-Curie No. 6, 141980 Dubna, Russia"},{"name":"Horia Hulubei National Institute for R&D in Physics and Nuclear Engineering, RO-077125 M\u0103gurele, Romania"},{"name":"Moscow Institute of Physics and Technology, Institutskiy Per. No. 9, 141701 Dolgoprudniy, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2872-7976","authenticated-orcid":false,"given":"Andrey","family":"Rogachev","sequence":"additional","affiliation":[{"name":"Joint Institute for Nuclear Research, Joliot-Curie No. 6, 141980 Dubna, Russia"},{"name":"Moscow Institute of Physics and Technology, Institutskiy Per. 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Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1042\/bj3540423","article-title":"Spectral and metal-binding properties of three single-point tryptophan mutants of the human transferrin N-lobe","volume":"354","author":"He","year":"2001","journal-title":"Biochem. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.jinorgbio.2017.12.012","article-title":"Binding of vanadium to human serum transferrin\u2014Voltammetric and spectrometric studies","volume":"180","author":"Azevedo","year":"2018","journal-title":"J. Inorg. Biochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/cbic.201402458","article-title":"Human Serum Transferrin Fibrils: Nanomineralisation in Bacteria and Destruction of Red Blood Cells","volume":"16","author":"Mukherjee","year":"2014","journal-title":"ChemBioChem"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/B978-0-12-416687-5.00027-0","article-title":"Metabolism of Iron and Heme","volume":"27","author":"Bhagavan","year":"2015","journal-title":"Essent. Med Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"119600","DOI":"10.1016\/j.saa.2021.119600","article-title":"Structural and molecular aspects of flavonoids as ligands for serum transferrin","volume":"254","author":"Sandu","year":"2021","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sandu, N., Popescu, A.I., and Chilom, C.G. (2021). Probing the interaction of fisetin with human serum transferrin via spectroscopic and molecular docking approaches. J. Biomol. Struct. Dyn., 1\u20137.","DOI":"10.1080\/07391102.2021.1934545"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1182\/blood.V43.5.767.767","article-title":"Evidence against transferrin as a binder of either vitamin B12 or folic acid","volume":"43","author":"Jacob","year":"1974","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/nnano.2012.237","article-title":"Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface","volume":"8","author":"Salvati","year":"2013","journal-title":"Nat. Nanotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"183903","DOI":"10.1063\/1.4967912","article-title":"Exchange bias in nano-ferrihydrite","volume":"120","author":"Balaev","year":"2016","journal-title":"J. Appl. Phys."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1134\/S1063783417030301","article-title":"Magnetic and resonance properties of ferrihydrite nanoparticles doped with cobalt","volume":"59","author":"Stolyar","year":"2017","journal-title":"Phys. Solid State"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1016\/j.ijbiomac.2020.08.242","article-title":"Ferrihydrite nanoparticles insights: Structural characterization, lactate dehydrogenase binding and virtual screening assay","volume":"164","author":"Chilom","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chilom, C.G., B\u0103lan, A., Sandu, N., B\u0103l\u0103\u015foiu, M., Stolyar, S., and Orelovich, O. (2020). Exploring the Conformation and Thermal Stability of Human Serum Albumin Corona of Ferrihydrite Nanoparticles. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249734"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"104851","DOI":"10.1016\/j.chemphyslip.2019.104851","article-title":"Ferrihydrite nanoparticles interaction with model lipid membranes","volume":"226","author":"Chilom","year":"2020","journal-title":"Chem. Phys. Lipids"},{"key":"ref_15","first-page":"1","article-title":"Biomedical Application of Biogenic Ferrihydrite Nanoparticles","volume":"62","author":"Chilom","year":"2017","journal-title":"Rom. Rep. Phys."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1021\/acsanm.7b00025","article-title":"Recent Advances Incorporating Superparamagnetic Nanoparticles into Immunoassays","volume":"1","author":"Ha","year":"2018","journal-title":"ACS Appl. Nano Mater."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.colsurfa.2017.11.062","article-title":"Paramagnetic colloidal ferrihydrite nanoparticles for MRI contrasting","volume":"539","author":"Sokolov","year":"2018","journal-title":"Colloids Surf. A Physicochem. Eng. Asp."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jmr.2012.11.029","article-title":"Magnetic Particle Imaging (MPI) for NMR and MRI researchers","volume":"229","author":"Saritas","year":"2013","journal-title":"J. Magn. Reson."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1080\/17425247.2019.1554647","article-title":"Magnetic iron oxide nanoparticles for drug delivery: Applications and characteristics","volume":"16","author":"Vangijzegem","year":"2019","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3109\/02656736.2014.913321","article-title":"Magnetic resonance imaging contrast of iron oxide nanoparticles developed for hyperthermia is dominated by iron content","volume":"30","author":"Wabler","year":"2014","journal-title":"Int. J. Hyperth."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1039\/C4NR04244A","article-title":"Recent progress in magnetic iron oxide\u2013semiconductor composite nanomaterials as promising photocatalysts","volume":"7","author":"Wu","year":"2015","journal-title":"Nanoscale"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"012003","DOI":"10.1088\/1742-6596\/994\/1\/012003","article-title":"Preparation, structure and magnetic properties of synthetic ferrihydrite nanoparticles","volume":"994","author":"Stolyar","year":"2018","journal-title":"J. Phys. Conf. Ser."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Macera, L., Taglieri, G., Daniele, V., Passacantando, M., and D\u2019Orazio, F. (2020). Nano-Sized Fe(III) Oxide Particles Starting from an Innovative and Eco-Friendly Synthesis Method. Nanomaterials, 10.","DOI":"10.3390\/nano10020323"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Stolyar, S., Kolenchukova, O., Boldyreva, A., Kudryasheva, N., Gerasimova, Y., Krasikov, A., Yaroslavtsev, R., Bayukov, O., Ladygina, V., and Birukova, E. (2021). Biogenic Ferrihydrite Nanoparticles: Synthesis, Properties In Vitro and In Vivo Testing and the Concentration Effect. Biomedicines, 9.","DOI":"10.3390\/biomedicines9030323"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/j.sjbs.2016.06.004","article-title":"Effects of hematite and ferrihydrite nanoparticles on germination and growth of maize seedlings","volume":"24","author":"Pariona","year":"2017","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_26","unstructured":"(2021, March 03). RCSB Protein Data Bank. Available online: www.rcsb.org\/structure\/1D3K."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The protein data bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucl. Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1110\/ps.9.1.49","article-title":"Crystal structures of two mutants (K206Q, H207E) of the N-lobe of human transferrin with increased affinity for iron","volume":"9","author":"Yang","year":"2008","journal-title":"Protein Sci."},{"key":"ref_29","unstructured":"(2021, March 03). Crystallography Open Database. Available online: https:\/\/wiki.crystallography.net\/cod\/citing."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S1004","DOI":"10.1007\/s003390101175","article-title":"The structure of six-line ferrihydrite Locality: Synthetic Sample: Defective refinement","volume":"74","author":"Jansen","year":"2002","journal-title":"Appl. Phys. A"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/978-1-4939-2269-7_19","article-title":"Small-molecule library screening by docking with PyRx","volume":"1263","author":"Dallakyan","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/pro.287","article-title":"Excited-state lifetime studies of the three tryptophan residues in the N-lobe of human serum transferrin","volume":"19","author":"James","year":"2009","journal-title":"Protein Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3614","DOI":"10.1002\/cphc.201402310","article-title":"Solvatochromic Study of Highly Fluorescent Alkylated Isocyanonaphthalenes, Their \u03c0-Stacking, Hydrogen-Bonding Complexation, and Quenching with Pyridine","volume":"15","author":"Nagy","year":"2014","journal-title":"ChemPhysChem"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jphotobiol.2005.12.017","article-title":"Steady-state fluorescence quenching applications for studying protein structure and dynamics","volume":"83","author":"Jenei","year":"2006","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lakowicz, R. (2007). Principles of Fluorescence Spectroscopy, Plenum Press.","DOI":"10.1007\/978-0-387-46312-4"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"64559","DOI":"10.1039\/C4RA11103F","article-title":"Spectroscopic and molecular modeling studies of human serum albumin interaction with propyl gallate","volume":"4","author":"Dolatabadi","year":"2014","journal-title":"RSC Adv."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chaves, O.A., Tavares, M.T., Cunha, M.R., Parise-Filho, R., Sant\u2019Anna, C.M.R., and Netto-Ferreira, J.C. (2018). Multi-Spectroscopic and Theoretical Analysis on the Interaction between Human Serum Albumin and a Capsaicin Derivative\u2014RPF101. Biomology, 8.","DOI":"10.3390\/biom8030078"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/13\/7034\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:27:16Z","timestamp":1760164036000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/13\/7034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,29]]},"references-count":39,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["ijms22137034"],"URL":"https:\/\/doi.org\/10.3390\/ijms22137034","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,29]]}}}