Family of Bioactive Heparin-Coated Iron Oxide Nanoparticles with Positive Contrast in Magnetic Resonance Imaging for Specific Biomedical Applications,Biomacromolecules

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Family of Bioactive Heparin-Coated Iron Oxide Nanoparticles with Positive Contrast in Magnetic Resonance Imaging for Specific Biomedical Applications
Biomacromolecules ( IF 5.5 ) Pub Date : 2017-09-22 00:00:00 , DOI: 10.1021/acs.biomac.7b00797
Hugo Groult ₁ , Nicolas Poupard ₁ , Fernando Herranz ₂ , Egle Conforto ₃ , Nicolas Bridiau ₁ , Fréderic Sannier ₁ , Stéphanie Bordenave ₁ , Jean-Marie Piot ₁ , Jesús Ruiz-Cabello ₂ , Ingrid Fruitier-Arnaudin ₁ , Thierry Maugard ₁

Affiliation

Unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH) are well-known for their anticoagulant properties. There is also currently a growing interest in using LMWH in targeted cancer therapy. In particular, several types inhibit heparanase, a key enzyme overexpressed in the tumor microenvironment that promotes angiogenesis progression and metastasis spreading. Here, we propose iron oxide nanoparticles (HEP-IONP) coated with different heparins of distinct anticoagulant/anti-heparanase activity ratios and suitable for positive contrast in magnetic resonance imaging. As a proof of concept, magnetic resonance angiography (MRA) was conducted in mice up to 3 h after intravenous administration. This new IONP-based positive contrast appropriate for clinic together with the long vascular circulating times can enable innovative theranostic applications if combined with the various bioactivities of the heparins. Indeed, we showed, using advanced in vitro tests, how HEP-IONP anticoagulant or anti-heparanase activities were maintained depending on the heparin species used for the coating. Overall, the study allowed presenting an IONP coated with a commercial LMWH (Lovenox) suggested as a theranostic translational probe for MRA diagnostic and treatment of thrombosis, and an antitumor IONP coated with a specific depolymerized heparin to be used in targeted therapy and diagnostic modalities.

中文翻译：

特定生物医学应用在磁共振成像中具有正对比的生物活性肝素涂层氧化铁纳米粒子家族。

普通肝素（UFH）和低分子量肝素（LMWH）因其抗凝血性能而闻名。目前，在靶向癌症治疗中使用LMWH的兴趣也越来越高。特别地，几种类型的抑制乙酰肝素酶，一种在肿瘤微环境中过表达的关键酶，可促进血管生成的进展和转移的扩散。在这里，我们建议氧化铁纳米粒子（HEP-IONP）涂有不同的肝素具有不同的抗凝/抗乙酰肝素酶活性比，并适合在磁共振成像中形成正对比。作为概念的证明，在静脉内给药后长达3小时的小鼠中进行了磁共振血管造影（MRA）。如果结合肝素的各种生物活性，这种适用于临床的基于IONP的新型阳性对比剂具有很长的血管循环时间，可以实现创新的治疗学应用。确实，我们展示了使用高级在体外测试中，如何维持HEP-IONP抗凝或抗乙酰肝素酶的活性取决于用于涂层的肝素种类。总体而言，该研究允许提出一种建议使用商业LMWH（Lovenox）涂层的IONP作为用于MRA诊断和治疗血栓形成的治疗学翻译探针，以及一种涂覆有特定解聚肝素的抗肿瘤IONP，用于靶向治疗和诊断方式。

更新日期：2017-09-23

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