Multidentate zwitterionic polymer modified ultrasmall iron oxide nanoparticles as a multimodal diagnostic imaging tool

The application of ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) as versatile diagnostic probes for biomedical imaging, including magnetic resonance imaging (MRI) and positron emission tomography (PET), requires hydrophilic and biocompatible surface coatings [1]. Novel coating strategies involving zwitterionic species limit nonspecific adsorption of biomolecules to the surface of nanoparticles and enable them to evade phagocytosis. This opens up promising routes for the development of clinically-approved nanoparticle-based theranostic agents with fewer off-target effects [2].We have generated a novel nanoparticle platform by introducing a zwitterionic polymer layer onto the magnetite particle surface (ZW-USPIONs). The ZW-USPIONs exhibit remarkable colloidal stabilities under extreme conditions, including high ionic strength, a wide pH range, and complex biological fluids. Furthermore, we have demonstrated that conjugation of biomolecules and/or bifunctional chelators for radiolabelling is feasible. Specifically, an epidermal growth factor (EGFR)-specific targeting vector and a 64Cu radiolabel for PET imaging have been
coupled to the carboxylic groups of ZW-USPIONs [3]. In vitro evaluation of the ZW-USPIONS using an MTT assay indicate low cytotoxicity in a range of human cells for nanoparticle concentrations up to 100 µg/mL. A very low degree nanoparticle-protein complex formation upon incubation of the ZW-USPIONs with human serum has been confirmed. Engineering the surface charge and functionalization of nanoparticles using multidentate zwitterionic polymers thus
provides a powerful strategy to optimise their surface properties for biological/medical applications, including as multimodal diagnostic imaging agents.

References
1. García KP, Zarschler K, Barreto JA, Hesse J, Spiccia L, Graham B, Stephan H, RSC Adv. 3, 22443 (2013).
2. García KP, Zarschler K, Barbaro L, Barreto JA, O'Malley W, Spiccia L, Stephan H, Graham B, Small. doi: 10.1002/smll.201303540 (2014).
3. Viehweger K, Barbaro L, García KP, Joshi T, Geipel G, Steinbach J, Stephan H, Spiccia L, Graham B. Bioconjugate Chem. doi: 10.1021/bc5001388 (2014).