INVESTIGATOR: Michael Antosh, University of Rhode Island
MENTOR: Wei Chen, University of Texas Arlington
THEME: Cancer

ABSTRACT: Copper-cysteamine nanoparticles are a recently discovered method for enhancing the effect of radiation therapy. When irradiated, these nanoparticles fluoresce and release reactive oxygen species that can cause extra damage to tumors. The extra damage to tumors allows for less radiation to be used, reducing side effects due to radiation and reducing the potential for cancer recurrences. These nanoparticles have recently been shown to reduce tumor size in mice but have only been tested in a small set of situations. 
This project proposes to investigate the effect of clinically important variables on the use of copper-cysteamine nanoparticles for radiation therapy enhancement, and to investigate novel imaging and treatment applications of the excess fluorescence produced by these particles. The hypothesis is that copper-cysteamine nanoparticles will be effective in clinically useful situations, and that these nanoparticles can be used in combination with dyes and photosensitizers to further increase effectiveness.
Specific Aim 1 is: Examine the range of effectiveness for copper-cysteamine nanoparticles, with a focus on clinically important variables. The goal of this aim is to determine the future clinical usefulness of copper-cysteamine nanoparticles by examining clinically important variables such as radiation energy, intravenous injections, damage to neighboring tissues and which types of cancers (cell lines) are most effectively treated. Measurements will include particle fluorescence (spectroscopy) as a function of radiation energy, tumor size after irradiation in a mouse xenograft model as a function of particle injection type (intratumoral vs intravenous), staining for DNA damage in mouse tissues that border tumors, distribution of particles across tissues in mice (ICP mass spectroscopy), and cell survival in vitro (clonogenic assay).
Specific Aim 2 is: Investigate two novel applications of copper-cysteamine nanoparticles. Copper-cysteamine nanoparticles produce excess fluorescence when irradiated, and this gives the possibility of combining these particles with a compound that absorbs the fluorescence and produces a further benefit to radiation therapy. The goal of this aim is to investigate the combination of copper-cysteamine nanoparticles with dyes for imaging and with additional photosensitizers for improved enhancement of radiation therapy (further damage to tumors). The photosensitizer bremachlorin and the dye pentamethine have spectra that match the output of copper-cysteamine nanoparticles; these substances will be tested in vitro for imaging capability (microscopy) and survival (clonogenic assay).

RELEVANCE: The use of copper-cysteamine nanoparticles in radiation therapy has the potential to lower the doses of radiation required to treat tumors, and lower radiation doses would decrease the side effects and cancer recurrences that result from radiation therapy. Copper-cysteamine nanoparticles may reduce required radiation doses even further when combined with photosensitizing molecules, which absorb light given off by the particles and produce further damage and may also be used for imaging with fluorescent dyes.