Project 4: Carbon Nanotube-based Microbeam Radiation Therapy for Human Brain Cancer We will develop a nanotechnology-enabled compact microbeam radiation therapy (MRT) system and translate the promising experimental radiotherapy from animal research to widespread clinical application. State-of-the-art radiotherapy today provides excellent benefits for many patients with radiosensitive cancers. However, these benefits greatly diminish for patients with radioresistant tumors, such as brain cancers. For these patients the radiafion, needed to eradicate the tumor is so toxic that it can cause intolerable damage to normal tissues. An ultimate radiotherapy approach should have high tissue type selectivity - it intrinsically eradicates tumor while leaving normal tissue function intact. MRT may be just such a radiotherapy approach. Convincing animal studies show that a single MRT treatment of ultrahigh dose (100s Gy) eradicates tumor without functional damage to normal tissue including that of the developing central nervous system. Despite its enormous potential MRT has not been used on human. There are two major bottlenecks In translating MRT from bench-side to bedside: 1) the lack of comprehensive understanding of the underlying mechanism and 2) the lack of accessible MRT irradiation devices. There are only synchrotron-based animal research MRT systems In the world, and no human MRT system exists today. Our goal is to develop a nanotechnology-based compact human MRT system for human brain tumors, especially glioblastoma (GBM), The poor control of GBM by current radiafion therapy is related to the dose limiting normal brain tissue damage such as brain necrosis. We hypothesize that MRT can effectively eradicate human brain tumors including GBM without severe normal brain function damage. We therefore propose to develop a compact MRT system for human brain cancers. The key technical challenge is to achieve the signature high dose rate at the microbeam spatial distribution. Our approach is to utilize the carbon nanotube based spatially distributed multi-beam field emission x-ray technology that was pioneered by our team. During the first CCNE project the technology blossomed into a technologically and commercially attractive approach for medical imaging and radiotherapy applications. In this second CCNE project we will use the CNT field emission technology to design the first nonsynchrotron-facility-based MRT system targeted for human brain cancer. We will validate that the CNTbased MRT radiation produces similar radiobiological effects on small animals as the synchrotron based MRT system. We will design, simulate, and validate major components of the compact human MRT system. Our target is to have the complete human MRT system design ready for device fabrication.

Public Health Relevance

Radioresistant tumors such as brain tumor Glioblastoma;radiafion damage to normal tissue;radiotherapy delivery technology development;and carbon nanotube field emission technology clincial application.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA151652-04
Application #
8540379
Study Section
Special Emphasis Panel (ZCA1-GRB-S)
Project Start
2013-08-01
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2013
Total Cost
$145,310
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Lucas, Andrew T; O'Neal, Sara K; Santos, Charlene M et al. (2016) A sensitive high performance liquid chromatography assay for the quantification of doxorubicin associated with DNA in tumor and tissues. J Pharm Biomed Anal 119:122-9
Kai, Marc P; Brighton, Hailey E; Fromen, Catherine A et al. (2016) Tumor Presence Induces Global Immune Changes and Enhances Nanoparticle Clearance. ACS Nano 10:861-70
Roode, Luke E; Brighton, Hailey; Bo, Tao et al. (2016) Subtumoral analysis of PRINT nanoparticle distribution reveals targeting variation based on cellular and particle properties. Nanomedicine 12:1053-62
Miao, Lei; Liu, Qi; Lin, C Michael et al. (2016) Targeting Tumor-associated Fibroblasts for Therapeutic Delivery in Desmoplastic Tumors. Cancer Res :
Li, Chengwen; Wu, Shuqing; Albright, Blake et al. (2016) Development of Patient-specific AAV Vectors After Neutralizing Antibody Selection for Enhanced Muscle Gene Transfer. Mol Ther 24:53-65
DeSimone, Joseph M; Mecham, Sue J; Farrell, Crista L (2016) Organic Polymer Chemistry in the Context of Novel Processes. ACS Cent Sci 2:588-597
Lecaros, Rumwald Leo G; Huang, Leaf; Lee, Tsai-Chia et al. (2016) Nanoparticle Delivered VEGF-A siRNA Enhances Photodynamic Therapy for Head and Neck Cancer Treatment. Mol Ther 24:106-16
Lu, Yao; Miao, Lei; Wang, Yuhua et al. (2016) Curcumin Micelles Remodel Tumor Microenvironment and Enhance Vaccine Activity in an Advanced Melanoma Model. Mol Ther 24:364-74
Sambade, Maria; Deal, Allison; Schorzman, Allison et al. (2016) Efficacy and pharmacokinetics of a modified acid-labile docetaxel-PRINT(®) nanoparticle formulation against non-small-cell lung cancer brain metastases. Nanomedicine (Lond) 11:1947-55
Rose, Tracy L; Deal, Allison M; Ladoire, Sylvain et al. (2016) Patterns of Bladder Preservation Therapy Utilization for Muscle-Invasive Bladder Cancer. Bladder Cancer 2:405-413

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