Magnetomotive ultrasound for nanomedicine: a mechanistic approach to detection, evaluation and safety assessment

Cancer is one of the leading causes of death worldwide, but reliable diagnosis and staging can contribute to optimal treatment planning, and is a crucial factor in reducing mortality and maintaining quality of life. Soft tissue mechanical properties are promising indicators of cancer that can be assessed non-invasively using functional imaging. Additionally, lymphatic involvement is considered a key aspect in staging of many types, including colorectal and breast cancer. Magnetomotive ultrasound, MMUS, is an imaging technique proposed for cancer staging and treatment. It relies on magnetically induced motion, transferred from a contrast agent to the tissue of interest. The tissue response to this perturbation is related to its mechanical properties, and thereby to cancer progression. Typically, the contrast agent consists of magnetic nanoparticles; These can be incorporated into microbubbles, that could allow for drug transport and site-specific delivery. Exploring these properties and possibilities of MMUS clarifies its clinical potential. The aim of this work was therefore to examine (a) the relation between tissue mechanical properties and magnetomotion, (b) the feasibility of magnetic microbubbles as a contrast agent and (c) the cellular response to magnetic nanoparticles and forces. Points (a) and (b) were addressed by comparing MMUS images conducted on real and phantom tissue to finite element analysis outputs; Transmission electron microscopy and quantitative cell based assays were used in exploring point (c). Magnetomotion was found to depend on tissue compressibility and elasticity, both potential cancer indicators. Tissue elasticity was also found to affect the tissue deformations induced by magnetic microbubbles. Furthermore, lymphatic drainage of magnetic microbubbles was demonstrated, validating their potential as a contrast agent in cancer imaging. Finally, cells were confirmed to take up nanoparticles, and no adverse effects of magnetic excitation was detected. In summary, there is merit to further development of MMUS for cancer diagnostics and treatment.