Family of Bioactive Heparin-Coated Iron Oxide Nanoparticles\nwith Positive Contrast in Magnetic Resonance Imaging for Specific\nBiomedical Applications

Abstract

Unfractionated\nheparin (UFH) and low-molecular-weight heparins (LMWH) are well-known\nfor their anticoagulant properties. There is also currently a growing\ninterest in using LMWH in targeted cancer therapy. In particular,\nseveral types inhibit heparanase, a key enzyme overexpressed in the\ntumor microenvironment that promotes angiogenesis progression and\nmetastasis spreading. Here, we propose iron oxide nanoparticles (HEP-IONP)\ncoated with different heparins of distinct anticoagulant/anti-heparanase\nactivity ratios and suitable for positive contrast in magnetic resonance\nimaging. As a proof of concept, magnetic resonance angiography (MRA)\nwas conducted in mice up to 3 h after intravenous administration.\nThis new IONP-based positive contrast appropriate for clinic together\nwith the long vascular circulating times can enable innovative theranostic\napplications if combined with the various bioactivities of the heparins.\nIndeed, we showed, using advanced <i>in vitro</i> tests,\nhow HEP-IONP anticoagulant or anti-heparanase activities were maintained\ndepending on the heparin species used for the coating. Overall, the\nstudy allowed presenting an IONP coated with a commercial LMWH (Lovenox)\nsuggested as a theranostic translational probe for MRA diagnostic\nand treatment of thrombosis, and an antitumor IONP coated with a specific\ndepolymerized heparin to be used in targeted therapy and diagnostic\nmodalities.