Design, synthesis and surface engineering of ultrasmall iron oxide nanoparticles for cancer imaging

There is currently a great interest in the application of nanoparticles for molecular imaging. This results in the development of both, organic and inorganic nanoparticles functionalized in a way that radionuclides, targeting ligands, and different biopolymers can be attached in order to provide an imaging signal. Ultrasmall superparamagnetic iron oxide (Fe3O4) nanoparticles (USPIOs) are one of the most widely studied nanomaterials. USPIOs possess unique magnetic properties that make them attractive candidates as advanced biomedical materials (1).
Furthermore, the biocompatibility of USPIOs makes them suitable to be used as multifunctional agents. They can serve as contrast agents for clinical use in magnetic resonance imaging (MRI), positron emission tomography (PET) and optical imaging (OI) (2).
This work aims at the development of new nanotracers based on USPIOs coated with a biodegradable polymer that are also decorated with agents for radiochemical and/or fluorescence imaging and Epidermal Growth Factor Receptor-specific ligands as targeting units (3).
The production of hydrophobic USPIOs has been achieved using thermal decomposition and monodisperse nanocrystals within a size of 4-5 nm were observed with Transmission electron microscopy (TEM) (4). The main limitation of using USPIOs for in vivo applications is their instability in water. Different biocompatible polymers such as polyvinylalcohol and polyacrylic acid have been tested for the hydrophilic coating of the iron oxide core to make them stable in aqueous solution (5). After an intensive physicochemical characterization including studies of their stability in water and several buffers, carboxymethyl polyvinyl alcohol (CMPVA) was chosen as the most suitable coating agent for the surface modification of USPIOs (6). The stability of the CMPVA-coated USPIOs was studied using Dynamic Light Scattering (DLS, Zetasizer/ Malvern).
Our first goal was to engineer and functionalize the surface of the hydrophilic USPIOs. This included the attachment of a fluorescent label to the shell. This enabled the USPIOs to be suitable for fluorescence imaging. Furthermore, preliminary radiolabeling studies (64Cu) have been undertaken using USPIOs decorated with functional copper chelating agents, such as NOTA. Radio-HPLC and Radio-TLC have been applied to get information about the labelling efficiency and stability of the 64Cu-labeled USPIOs.
From our point of view, the generated nanoparticles possess promising features as novel imaging agents for in vivo cancer diagnostics.

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2. Laurent, S., et al., Chemical Reviews, 108(6): p. 2064-211, 2008.
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4. Park, J., et al., Nat Mater, 3(12): p. 891-895, 2004.
5. Zhang, F., et al., Small, 7(22): p. 3113-3127, 2011.
6. Liong, M., et al., Advanced Materials, 22(45): p. 5168-5172, 2010.