{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T19:32:26Z","timestamp":1789241546405,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Assignment of the Ministry of Health of the Russian Federation","award":["056-00065-24-02"],"award-info":[{"award-number":["056-00065-24-02"]}]},{"name":"State Assignment of the Ministry of Health of the Russian Federation","award":["122040600057-3"],"award-info":[{"award-number":["122040600057-3"]}]},{"name":"State Assignment of the Lomonosov Moscow State University","award":["056-00065-24-02"],"award-info":[{"award-number":["056-00065-24-02"]}]},{"name":"State Assignment of the Lomonosov Moscow State University","award":["122040600057-3"],"award-info":[{"award-number":["122040600057-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Iron deficiency anemia (IDA) remains a global health challenge. This study pioneers the use of humic substances (HS) as natural, biocompatible macroligands to develop safer and more effective nanoferrotherapeutics. We synthesized a series of nanoscale Fe(III) oxyhydroxide complexes stabilized by different HS, employing various solvents (ethanol, isopropanol, and acetone) and precipitation methods to isolate fractions with optimized properties. The nanocomposites were comprehensively characterized using inductively coupled plasma atomic emission spectrometry, total organic carbon analysis, X-ray diffraction, transmission electron microscopy, and M\u00f6ssbauer spectroscopy. Cytotoxicity and iron bioavailability of all HS-Fe(III) formulations were assessed in Caco-2 intestinal epithelial cells. The type of HS and precipitation conditions significantly influenced the nanocomposites\u2019 properties, yielding spherical nanoparticles (1\u20132 nm) of ferrihydrite or goethite. Physicochemical analysis confirmed that solvent-driven fractionation effectively tailored the nanocomposites\u2019 size, crystallinity, and elemental composition. All HS-Fe(III) formulations demonstrated exceptional cytocompatibility, starkly contrasting the significant cytotoxicity of the reference drug Ferrum Lek\u00ae. Several complexes, particularly CHSFe-Et67, surpassed Ferrum Lek\u00ae in cellular iron uptake efficiency. We conclude that HS are a highly promising platform for developing effective and safe iron-delivery nanoferrotherapeutics, leveraging their natural polyfunctionality to enhance bioavailability and mitigate toxicity.<\/jats:p>","DOI":"10.3390\/nano15181400","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T14:23:50Z","timestamp":1757600630000},"page":"1400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Humics-Functionalized Iron(III) Oxyhydroxides as Promising Nanoferrotherapeutics: Synthesis, Characterization, and Efficacy in Iron Delivery"],"prefix":"10.3390","volume":"15","author":[{"given":"Anastasiya M.","family":"Zhirkova","sequence":"first","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, Leninskiye Gory 1-3, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1973-8983","authenticated-orcid":false,"given":"Maria V.","family":"Zykova","sequence":"additional","affiliation":[{"name":"Pharmaceutical Faculty, Siberian State Medical University, Tomsk 634050, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6714-1938","authenticated-orcid":false,"given":"Evgeny E.","family":"Buyko","sequence":"additional","affiliation":[{"name":"Pharmaceutical Faculty, Siberian State Medical University, Tomsk 634050, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina A.","family":"Ushakova","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, Leninskiye Gory 1-3, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir V.","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Pharmaceutical Faculty, Siberian State Medical University, Tomsk 634050, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6557-2753","authenticated-orcid":false,"given":"Denis A.","family":"Pankratov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, Leninskiye Gory 1-3, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6104-4782","authenticated-orcid":false,"given":"Elena V.","family":"Udut","sequence":"additional","affiliation":[{"name":"Pharmaceutical Faculty, Siberian State Medical University, Tomsk 634050, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyudmila A.","family":"Azarkina","sequence":"additional","affiliation":[{"name":"Pharmaceutical Faculty, Siberian State Medical University, Tomsk 634050, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6381-1327","authenticated-orcid":false,"given":"Sergey R.","family":"Bashirov","sequence":"additional","affiliation":[{"name":"Pharmaceutical Faculty, Siberian State Medical University, Tomsk 634050, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4374-6422","authenticated-orcid":false,"given":"Evgenii V.","family":"Plotnikov","sequence":"additional","affiliation":[{"name":"Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, Tomsk 634050, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9034-4733","authenticated-orcid":false,"given":"Alexey N.","family":"Pestryakov","sequence":"additional","affiliation":[{"name":"Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, Tomsk 634050, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2153-7945","authenticated-orcid":false,"given":"Mikhail V.","family":"Belousov","sequence":"additional","affiliation":[{"name":"Pharmaceutical Faculty, Siberian State Medical University, Tomsk 634050, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9084-7851","authenticated-orcid":false,"given":"Irina V.","family":"Perminova","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, Leninskiye Gory 1-3, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e000759","DOI":"10.1136\/bmjgast-2021-000759","article-title":"Iron deficiency anaemia: Pathophysiology, assessment, practical management","volume":"9","author":"Kumar","year":"2022","journal-title":"BMJ Open Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wang, L., Liang, D., Huangfu, H., Shi, X., Liu, S., Zhong, P., Luo, Z., Ke, C., and Lai, Y. 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