Cancer Therapy based on Core-Shell Iron-Iron Oxide Nanowires

Abstract

Nanomaterials have been widely investigated for improving the treatment of diseases acting as vectors for diverse therapies and as diagnostic tools. Iron-based nanowires possess promising potential for biomedical applications due to their outstanding properties. The combination of different therapeutic and diagnostic strategies into one single platform is an approach for more efficient and safer treatments. In this thesis, I investigate the application of iron-iron oxide core-shell nanowires as therapeutic agents for cancer treatment. In particular, a novel method for multimodal cancer cell destruction was developed combining the optical, magneto-mechanical and chemotherapeutic properties of functionalized nanowires. By functionalizing the nanowires with doxorubicin through a pH-sensitive linker, the first treatment modality was achieved by selective intracellular drug release. The second treatment modality utilizes the mechanical disturbance exerted by the nanowires upon the application of a low-power alternating magnetic field. The third treatment modality exploits the capability of the nanowires to transform optical energy, absorbed from near-infrared irradiation, into heat. The efficiency of the three treatment modalities both independently and combined were tested in breast cancer cells with near complete cell death (90%). The combination of the different strategies can potentially reduce side effects and treatment time. Additionally, I studied the potential of these iron-iron oxide core-shell nanowires as diagnostic tools, included in the Appendix of this dissertation. Specifically, I studied their capability to act as magnetic resonance imaging contrast agents for cell labeling, detection and tracking. Therein, a high performance as T2 contrast agents was confirmed evaluating the effect of oxidation and surface coatings on the T2 contrast in the tailored transverse relaxivities. The detection of nanowire-labeled cancer cells was demonstrated in T2-weighted images of cells implanted in tissue-mimicking phantoms and in mouse brain. Labeling the cells with nanowires enabled high-resolution cell detection after in vivo implantation (~10 cells) over a minimum of 40 days. The capability of these magnetic nanowires of being remotely controllable and detectable make them an attractive option in the treatment and diagnosis of cancer and in cell therapy. Future directions include preclinical studies for testing the nanowire-based photothermal therapy for tumor ablation.