The purpose of this research is to engineer hybrid theranostic nanoparticles Fe<sub>3</sub>O<sub>4</sub>@DA-BSA/H, see Figure 1. The inorganic core is super paramagnetic iron oxide nanoparticles (Fe3O4, SPIONs) while the organic coating layers are heparin derivatives (H) and bovine serum albumin (BSA). H and BSA were previously covalently conjugated to dopamine (DA) enabling their further anchoring to the SPIONs by ligand-exchange on Fe@oleate. SPIONs were selected due to their capability to act as MRI negative contrast agents. Therapeutic functions are attributed to two H, low molecular weight heparin (LMWH) and glycol split heparin (gsH) that possess antimetastatic and antiangiogenetic activities mainly through heparanase inhibition with no/reduced anticoagulant activity (gsH/LMWH), see Figures 1 and 2. Figure 2 reports how heparan sulfate (HS) fragments released by heparanase activate growth factors (FGF). HS enzymatic degradation leads to disassembly of the extracellular matrix (ECM) and is therefore involved in tissue remodelling and cell migration, including cancer angiogenesis and metastasis. Furthermore, as heparanase is overexpressed by the environment of a large number of tumors, its inhibitors could undergo an active targeting transport to the tumor mass. DA-BSA and DA-H conjugates were prepared via condensation reaction using carbodiimide (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide). DA-BSA conjugates were analyzed via MALDI-TOF to obtain the degree of substitution, which can be modulated in the range 25-40 DA per BSA. DA-H conjugates were analyzed via FT-IR to ensure the conjugation. NMR studies assessed that the ratio between DA: monosaccharide can reach 1:4.

Design and preparation of heparin-superparamagnetic iron oxide nanoparticles aimed at biomedical applications

ACS Fall 2021

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