Targeted Gold Nanoparticles (AuNPs) for Potent Alpha-Particle Radiotherapy of Brain Cancer
Abstract
Brain cancer is an FY18 PRCRP topic area and it has the highest first-year cost (>$120,000) among all cancers. Glioblastoma (GBM) is the most common brain cancer, and it has an overall survival of only 15 months even after aggressive treatment including surgery, radiation therapy, and chemotherapy. Although promising, current immunotherapy has shown limited therapeutic improvement on GBM patients. My goal is to develop novel therapies to improve survival time and reduce healthcare cost for brain cancer patients. I already have extensive research experience in cancer nanomedicine, applying nanotechnology in cancer applications. For my Ph.D. thesis, I developed a multifunctional gold nanostar probe for cancer detection and photothermal therapy. I have applied the multifunctional nanoprobe for brain cancer imaging by PET/CT and treatment with photothermal therapy. Furthermore, I also combined the nanoparticles-mediated photothermal therapy with the checkpoint immunotherapy for synergistic brain cancer treatment. I have experience in cancer imaging and therapy using nanotechnology. The Horizon Award will provide me with valuable support to advance my career in cancer research. I plan to take comprehensive training as a radiochemist on Astatine-211 (211At) isotope production, processing, purification, and radiolabeling. Furthermore, I also plan to take training on in vitro binding affinity and toxicity assay as well as in vivo pharmacokinetics, biodistribution, and survival studies. My unique training experience in both nanotechnology and radiochemistry will make me capable to develop novel methods to treat aggressive brain cancer. Based on my Researcher Development Plan, I will be co-advised by two prestigious experts, Dr. Tuan Vo-Dinh and Dr. Michael Zalutksy. I plan to move forward toward an independent cancer researcher by taking full advantage of the Horizon Award opportunity. As a principal investigator, I will choose a unique cancer research direction, propose a novel strategy to solve most pressing challenges in cancer management and develop a novel therapy for effective brain cancer treatment. After this valuable training, I will be able to not only enhance my expertise with radiochemistry but also work as an independent principal investigator to achieve my goals in cancer research. My ultimate goal is to find better treatments for cancer; brain cancer in particular. My proposed novel targeted alpha-particle radiotherapy with gold nanoparticles has the advantage of potent cancer-killing effect without compromise by harsh tumor microenvironment, simple preparation process, and high treatment specificity fulfilled by cancer targeting and short killing range of just several cells. Furthermore, the therapeutic radioisotope delivery process can be monitored in real time, which enable us to customize the treatment plan to improve therapeutic outcomes. This method has the promise to improve brain cancer patients survival time and reduce the financial burden. Moreover, it can not only be used for brain cancer treatment but also has the potential to be applied for other deadly cancer diseases like breast cancer and prostate cancer. One potential risk is radiation exposure to normal organs. However, quick renal clearance would largely mitigate this concern. If our preliminary studies in mice are successful, the next step would be large animal (dogs or non-human primates) studies and an early phase human clinical trial. 211At has been tested in clinical trials led by Professor Michael Zalutsky (co-Mentor) at Duke University. In addition, since gold nanoparticles are generally considered to be non-toxic, we believe that using a small amount of gold nanoparticles in humans should be safe or without a significant safety concern. Therefore, if this treatment appears to work well in our large animal models, we believe that it should be relatively straightforward to take targeted alpha-particle radiotherapy with gold nanopa
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910684
Entities
People
- Yang Liu
Organizations
- Duke University
- United States Army