The objective of this research is to develop a new cancer therapy that uses non-thermal irreversible electroporation (N-TIRE) with carbon nanotubes (CNTs). N-TIRE is a new, minimally invasive focal ablation technique that uses low energy (intense, but short) electric pulses to treat targeted tissue for approximately 1 minute. These pulses kill cells within the targeted area without damaging the surrounding tissue. However, since N-TIRE is a focal ablation technique, it does not selectively kill infiltrative cells beyond the tumor margin without affecting surrounding tissue. We hypothesize that incorporating CNTs into N-TIRE therapy can enable selective therapy of infiltrative cells capable of metastasis. When exposed to an electric field, CNTs amplify the field at their CNT tip. Localized amplification of these fields should induce N-TIRE in adjacent cells from relatively small electric fields, without affecting healthy surrounding cells. This proposal will investigate the impact of N-TIRE protocols and CNT properties on the electric field, temperature distribution, and cellular/tissue response through the following objectives: 1) Determine the cellular response to N-TIRE in combination with a variety of CNT embodiments 2) Create a multi-scale, multi-physics computational model of N-TIRE with CNTs to predict the tissue response to N-TIRE protocols and CNT properties 3) Implement optimal CNT-mediated N-TIRE protocols and measure the in vivo response of brain tumors.
The intellectual merit of the proposed activity will be the development of a comprehensive understanding of the impact of varying N-TIRE parameters in combination with different CNT embodiments with antibody targeting on therapy effectiveness. Defining the relationship between N-TIRE parameters and CNT properties on cellular injury will provide enormous insight to guide design of more effective cancer therapies, which enhance tumor destruction and minimize tumor recurrence. If combinatorial N-TIRE/CNT therapy proves to be effective, it will possess significant advantages over many current cancer treatments and this research will provide the necessary data for first stage development of this therapy.
The broader impacts of the proposed study include the determination of optimal N-TIRE/CNT parameters to effectively and selectively treat both the primary tumor and the infiltrative cancer cells, thereby eliminating the likelihood of tumor recurrence and metastasis. Although this approach could be utilized to treat a number of cancers including prostate, liver, kidney and pancreatic, brain cancer will serve as our model. Research contained in this project will provide motivation for related topics taught within the investigator's courses and permit the opportunity to augment the course with an interactive laboratory component focused on the converging fields of electroporation, nanotechnology, and bioheat transfer. This research will enable opportunities for numerous students to gain experience in experimental design, engineering, and cell biology at the graduate and undergraduate level. Scholastically strong undergraduate students from underrepresented groups will be recruited to perform research during the summer through two summer programs directed by the investigator. We will also develop a joint workshop for bioengineering students and medical students to discuss the synergistic aspects of engineering, experimental biology, and veterinary and clinical medicine to design new innovative therapies.
