The presence of imbedded gold nanoparticles (GNPs) can amplify tumor tissue’s sensitivity to radiation therapy and potentially alter the course of treatment for many different types of cancer. Can focused ultrasound induce hyperthermia to improve the imbedding process? In the final report from a 2013 High-Risk Track Foundation Research Award submitted by MD Anderson Cancer Center Principle Investigators Sunil Krishnan, MD, and Jason Stafford, PhD, the answer is “Yes.”
The project, entitled “Deep Penetrating Triggered Release Nanoparticles as Tumor Radiosensitizers,” ed whether focused ultrasound–induced hyperthermia (heat) could introduce GNPs into tissue to make the tissue more responsive to radiotherapy treatment. The study:
- Determined how GNP cells are activated by focused ultrasound’s heat.
- Distinguished between radiosensitization due to heat or due to the release of the GNPs.
- Optimized GNP-based radiosensitization.
Irradiation of GNP-filled tumors enhances radiotherapy by producing secondary electron showers that emanate from the gold particle–radiation interactions. It is challenging to load tumors with enough gold to reach the radiotherapy’s true potential, so the project attempted to use the heat from focused ultrasound to create a higher accumulation of gold within tumors, particularly deep within the core of the tumors. To achieve this, Drs. Krishnan and Stafford encapsulated the GNPs in temperature-sensitive liposomes that will deposit their payload when they encounter the focal heating of the focused ultrasound.
“I have heard much discussion of focused ultrasound–induced radiosensitization,” said Matt Eames, PhD, the Foundation’s Director of Extramural Research. “Dr. Krishnan’s project looks to the next step by capitalizing on drug delivery techniques to focally deposit GNPs that enhance radiotherapy through the physics of particle-radiation interactions.”
Study Results
The team used three different strategies to evaluate GNP penetration into tumors. These methods individually and collectively confirmed that focused ultrasound–induced hyperthermia did result in deep penetration of GNPs within tumors in a mouse model, and the resulting deep penetration of the GNPs into the tumors did contribute to the radiosensitization. In other words, the hyperthermia created the deep penetration of the GNPs, and the deep penetration amplified the radiosensitization.
The results of this study were presented in the Focused Ultrasound Opportunities in Radiation Oncology session of the Society for Thermal Medicine’s Annual Meeting held during May 7-1, 2014 in Minneapolis.
Future Plans
Small quantities of gold that are deep within the tumor increase radiosensitization, but could their movement deeper into the cell further enhance the effect? The researchers now plan to alter the structure of the GNPs in a way that would allow them to move even deeper into the cells (closer to the DNA) and further improve the radiosensitization. They also theorize that chemotherapy agents could also be similarly altered, heated, and embedded deep within the tumor cells.
For follow-on funding, Drs. Krishnan and Stafford submitted a proposal to the National Cancer Institute as one of the main projects in a U54 Nano-Center grant.