Biofunctionalization of Magnetic Nanomaterials.

Magnetic nanomaterials have received great attention in different biomedical applications. Biofunctionalizing these nanomaterials with specific targeting agents is a crucial aspect to enhance their efficacy in diagnostics and treatments while minimizing the side effects. The benefit of magnetic nanomaterials compared to non-magnetic ones is their ability to respond to magnetic fields in a contact-free manner and over large distances. This allows to guide or accumulate them, while they can also be monitored. Recently, magnetic nanowires (NWs) with unique features were developed for biomedical applications. The large magnetic moment of these NWs enables a more efficient remote control of their movement by a magnetic field. This has been utilized with great success in cancer treatment, drug delivery, cell tracing, stem cell differentiation or magnetic resonance imaging. In addition, the NW fabrication by template-assisted electrochemical deposition provides a versatile method with tight control over the NW properties. Especially iron NWs and iron-iron oxide (core-shell) NWs are suitable for biomedical applications, due to their high magnetization and low toxicity. In this work, we provide a method to biofunctionalize iron/iron oxide NWs with specific antibodies directed against a specific cell surface marker that is overexpressed in a large number of cancer cells. Since the method utilizes the properties of the iron oxide surface, it is also applicable to superparamagnetic iron oxide nanoparticles. The NWs are first coated with 3-aminopropyl-tri-ethoxy-silane (APTES) acting as a linker, which the antibodies are covalently attached to. The APTES coating and the antibody biofunctionalization are proven by electron energy loss spectroscopy (EELS) and zeta potential measurements. In addition, the antigenicity of the antibodies on the NWs is tested by using immunoprecipitation and western blot. The specific targeting of the biofunctionalized NWs and their biocompatibility are studied by confocal microscopy and a cell viability assay.

Functionalization of Magnetic Nanowires for Active Targeting and Enhanced Cell-Killing Efficacy.

Conventional chemotherapy and radiation therapy are often insufficient in eliminating cancer and are accompanied by severe side effects, due to a lack in the specificity of their targeting. Magnetic iron nanowires have made a great contribution to the nanomedicine field because of their low toxicity and ease of manipulation with the magnetic field. Recently, they have been used in magnetic resonance imaging and wireless magnetomechanical and photothermal treatments. The addition of active targeting moieties to these nanowires thus creates a multifunctional tool that can boost therapeutic efficacies through the combination of different treatments toward a specific target. Colon cancer is the third most commonly occurring cancer, and 90 ± 2.5% of colon cancer cells express the glycoprotein CD44. Iron nanowires with an iron oxide surface are biocompatible, multifunctional materials that can be controlled by magnetic fields and heated by laser irradiation. Here, they were functionalized with anti-CD44 antibodies and used in a combination therapy that included magnetomechanical and photothermal treatments on colon cancer cells. The functionalization resulted in a 3-fold increase of nanowire internalization in colon cancer cells compared to control cells and did not affect the antigenicity and magnetic properties. It also increased the efficacy of killing from 35 ± 1% to more than 71 ± 2%, showing that the combination therapy was more effective than individual therapies alone.