Targeted Prostate Tumor Ablation Using Engineered Gold Nanorods

Nanotechnology is emerging as a major high-tech industry with applications in alternative energy solutions, transportation, electronics, and healthcare. In 2001 the National Nanotechnology Initiative (NNI) was established, placing nanotechnology research at the top of the list of emerging technologies being developed in the United States. This is particularly the case in the fields of cancer therapy and detection where so-called 'nanoconstructs' can interact with and manipulate cancer due to their subcellular size. Despite its tremendous potential, advancements at the interface of nanotechnology and medicine (termed nanomedicine) have been slow due to the lack of sufficient scientists and engineers with the multidisciplinary training necessary to bring the technology from the benchtop to the marketplace and, ultimately, the patient clinic. The PI plans to develop a career in prostate cancer nanotechnology that will be multidisciplinary in science, engineering, medicine, and business. To facilitate training in nanotechnology and cancer treatment the PI will receive guidance under his primary mentor, Dr. Hamid Ghandehari, while pursuing a Ph.D. degree in Bioengineering. Dr. Ghandehari, Utah Science Technology and Research (USTAR) faculty and co-founder of the Nano Institute of Utah, will train the PI in all disciplines particularly related to laboratory synthesis, characterization, and targeting of nanoconstructs to prostate cancer cells for the purposes of the proposed research plan. During this time the PI will also receive guidance at the University of Utah's Huntsman Cancer Institute for training in how technologies such as nanotechnology can be brought from the benchtop to the patient clinic.

Termed photothermal therapy, one potential application of nanotechnology in prostate cancer therapy pertains to the unique optical properties of gold nanorods to convert light energy into heat. Following intravenous injection of gold nanorods, a fiber optic laser can be inserted at the site of the tumor and then turned on to excite the nanoparticles and produce enough heat to kill all cancerous cells. Though sound in theory, complete destruction of large tumors without harmful side effects is difficult because tissue absorbs light to a high extent, thereby requiring high laser energies to induce sufficient heating. Therefore, it is important to specifically target the gold nanorods to vulnerable regions of prostate tumors so that the energy required for killing the tumor is minimized. Of particular interest, the cell surface of the malignant cells and surrounding tumor vasculature has been identified as potential targets of vulnerability. Destruction of the tumor's vasculature, which supplies it all necessary nutrients to survive, would starve the tumor and ultimately cause death. Also, direct heating of the cancerous cells would have this effect directly. To this end, the PI is proposing a novel strategy using angiogenesis and glucose receptor-targeted gold nanoparticles to effectively deliver lethal doses of heat specifically to the tumor. Both of these targeting strategies have been proven with other systems, though their application with gold nanoparticles and photothermal therapy is novel.

Although this form of therapy is not likely to eradicate all forms of prostate cancer in all patients, it has applications as a low-cost, minimally invasive first line of defense therapy before more aggressive therapies are tried such as surgery or radiation and chemotherapy. Patients with nonmetastatic prostate cancer could potentially walk into a clinic and receive harmless injections of targeted gold nanorods. These patients would then have a relatively simple and therefore low-cost fiber optic laser inserted through their urethra or anus and directed at the prostate tumor to excite and heat all targeted nanorods. The novelty of the proposed strategy lies in the potential to increase the lethality of photothermal therapy by specifically targeting the gold nanorods to vulnerable regions of the tumor. It is expected that outcomes of treatment would be available within a few days because the extent of tumor death would occur shortly after treatment.