Investigator: Michael Antosh, University of Rhode Island

Scientific Theme: Cancer

Abstract: The broad objective of this project is to improve the treatment of cancer by enhancing the effect of radiation on cancer. If radiation can be made to have a greater impact on cancer, less radiation can be used, which would reduce side effects to patients. Alternatively, more effective cancer treatment can be had for the same radiation doses currently used. Thus, the health related impact of this project is potentially both a reduction in side effects from radiation therapy in cancer patients as well as an increase in radiation effectiveness for cancer treatment.

This project aims to improve the effectiveness of radiation using two types of nanoparticles: gold, and copper-cysteamine. Gold nanoparticles absorb more radiation than human tissue at certain photon energies (approximately 10 keV to 1 MeV), and gold atoms can emit extra electrons after irradiation via the Auger Effect (when an excited atom releases its extra energy through the release of an electron). Copper-cysteamine nanoparticles release poisonous singlet oxygen when irradiated, which can cause further damage to cancer cells. The impact of both types of nanoparticles should be increased by targeting the gold nanoparticles to cancer, using the pH-sensitive cancer targeting molecule called pH-Low Insertion Peptide (pHLIP).

One of the two major goals of this project is to explore the effect of targeted gold nanoparticles on radiation therapy in a mouse model of cancer. Survival and tumor size will be tracked as a function of time after irradiation. The effects of radiation dose, amount of nanoparticles and size of nanoparticles on the treatment of the mice will be examined by tracking tumor size and survival as a function of time after irradiation. Additionally, the distribution of gold inside the mouse will be determined, both between organs and inside cells. This knowledge is particularly useful for potential future clinical applications.

The second major goal of this project is to explore the effect of targeted copper-cysteamine nanoparticles on radiation therapy in a mouse model of cancer. Survival and tumor size will be tracked as a function of time after irradiation, for mice given treatments of no particles, targeted particles or non-targeted particles.

The results of these experiments have the potential to be very helpful, both in terms of providing new scientific and technical knowledge and as the foundation of applications for R01 grants. In the future, hopefully one or both of these treatments can become clinically useful as a way of enhancing radiation therapy for human patients.

Human Health Relevance:  The goal of this project is to improve the effectiveness of radiation treatments to cancer patients. This means that a given dose of radiation would cause more damage to cancer than currently happens. This could make radiation treatments more likely to work, which could save the lives of cancer patients, and it would allow for less radiation to be used on patients who are at risk from radiation side effects.