(624c) Biomaterial Scaffolds for Destruction of Disseminated Cancer Cells through Non-Invasive Local Hyperthermia

Breast cancer is the most common type of cancer affecting women in the U.S., with the main cause of death resulting not from the primary tumor but from metastasis to vital organs. Currently, there are very few therapeutic options for treatment of metastatic disease, as it often remains undetected until the burden of disease is too high. Focal therapies, such as localized application of heat, have shown promise in the treatment of various types of tumors. While these strategies are effective at treating solid tumors, they have not been successfully applied to disseminated tumor cells. We have previously developed microporous polymeric biomaterials that attract metastasizing breast cancer cells in vivo early in tumor progression. Recruitment of disseminating cells to the scaffold results in reduced tumor burden in the lung and liver, typical metastatic sites. In order to enhance the therapeutic potential of these scaffolds, we sought to modify them such that non-invasive local hyperthermia could be applied to disseminating cells by collecting them at a specific site in the body. To accomplish this goal, we incorporated metal disks into polycaprolactone scaffolds to generate heat through electromagnetic induction by an oscillating magnetic field within a radiofrequency coil. The amount of heat generation was modulated by varying the size of the metal disk or the strength and frequency of the magnetic field. For a magnetic field strength of 10 kA/m and a frequency of 190 kHz, we were able to vary the resulting temperature elevation from 4 to 30 °C by changing the diameter of the metal disk. When implanted subcutaneously in mice, the scaffolds were biocompatible and became properly integrated with the host tissue. In order to identify optimal conditions for in vivo application of scaffold-based focal therapy, fully integrated scaffolds were removed from mice three weeks post-implantation. Ex vivo characterization of heat transfer dynamics within the tissue-laden biomaterial was performed through a combination of mathematical modeling and experimental measurements of the temperature distribution throughout the scaffold upon inductive heating. To verify that inductive heating could kill cells within the scaffold, we demonstrated that increasing the temperature of the tissue from 37 to 52 ºC for 10 seconds was sufficient to cause an 85% reduction in metabolic activity of the tissue, as determined using a WST-1 viability assay. This electromagnetic induction strategy can be readily applied non-invasively and repeatedly in vivo. The combination of capturing metastatic cells and destroying them very early in disease progression has the potential to dramatically improve the treatment of metastatic disease.