{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T11:24:48Z","timestamp":1776425088954,"version":"3.51.2"},"reference-count":64,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research (MIUR)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were engineered with an organic coating composed of low molecular weight heparin (LMWH) and bovine serum albumin (BSA), providing heparin-based nanoparticle systems (LMWH@SPIONs). The purpose was to merge the properties of the heparin skeleton and an inorganic core to build up a targeted theranostic nanosystem, which was eventually enhanced by loading a chemotherapeutic agent. Iron oxide cores were prepared via the co-precipitation of iron salts in an alkaline environment and oleic acid (OA) capping. Dopamine (DA) was covalently linked to BSA and LMWH by amide linkages via carbodiimide coupling. The following ligand exchange reaction between the DA-BSA\/DA-LMWH and OA was conducted in a biphasic system composed of water and hexane, affording LMWH@SPIONs stabilized in water by polystyrene sulfonate (PSS). Their size and morphology were investigated via dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The LMWH@SPIONs\u2019 cytotoxicity was tested, showing marginal or no toxicity for samples prepared with PSS at concentrations of 50 \u00b5g\/mL. Their inhibitory activity on the heparanase enzyme was measured, showing an effective inhibition at concentrations comparable to G4000 (N-desulfo-N-acetyl heparin, a non-anticoagulant and antiheparanase heparin derivative; Roneparstat). The LMWH@SPION encapsulation of paclitaxel (PTX) enhanced the antitumor effect of this chemotherapeutic on breast cancer cells, likely due to an improved internalization of the nanoformulated drug with respect to the free molecule. Lastly, time-domain NMR (TD-NMR) experiments were conducted on LMWH@SPIONs obtaining relaxivity values within the same order of magnitude as currently used commercial contrast agents.<\/jats:p>","DOI":"10.3390\/molecules27207116","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T08:19:06Z","timestamp":1666599546000},"page":"7116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Heparin\u2013Superparamagnetic Iron Oxide Nanoparticles for Theranostic Applications"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1232-8578","authenticated-orcid":false,"given":"Nicol\u00f2","family":"Massironi","sequence":"first","affiliation":[{"name":"Department of Chemistry, Materials and Chemical Engineering \u201cGiulio Natta\u201d, Politecnico di Milano, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3428-5668","authenticated-orcid":false,"given":"Miriam","family":"Colombo","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences, University of Milano Bicocca, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cesare","family":"Cosentino","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Chimiche e Biochimiche \u201cGiuliana Ronzoni\u201d, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Fiandra","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences, University of Milano Bicocca, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7777-9820","authenticated-orcid":false,"given":"Michele","family":"Mauri","sequence":"additional","affiliation":[{"name":"Department of Materials Science, University of Milano Bicocca, 20125 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmina","family":"Kayal","sequence":"additional","affiliation":[{"name":"Rappaport Faculty of Medicine, Israel Institute of Technology, Haifa 2611001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9234-7778","authenticated-orcid":false,"given":"Filippo","family":"Testa","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences, University of Milano Bicocca, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2077-1203","authenticated-orcid":false,"given":"Giangiacomo","family":"Torri","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Chimiche e Biochimiche \u201cGiuliana Ronzoni\u201d, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0918-0808","authenticated-orcid":false,"given":"Elena","family":"Urso","sequence":"additional","affiliation":[{"name":"Istituto di Ricerche Chimiche e Biochimiche \u201cGiuliana Ronzoni\u201d, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6547-9276","authenticated-orcid":false,"given":"Elena","family":"Vismara","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Materials and Chemical Engineering \u201cGiulio Natta\u201d, Politecnico di Milano, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Israel","family":"Vlodavsky","sequence":"additional","affiliation":[{"name":"Rappaport Faculty of Medicine, Israel Institute of Technology, Haifa 2611001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s10555-020-09931-5","article-title":"Current Methods in Translational Cancer Research","volume":"40","author":"Lee","year":"2021","journal-title":"Cancer Metastasis Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"160902","DOI":"10.1063\/5.0085202","article-title":"Magnetic Nanoparticles in Theranostic Applications","volume":"131","author":"Coene","year":"2022","journal-title":"J. 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