Curative treatment of local and/or regional breast cancer requires surgery and adjuvant therapy such as thermotherapy. In thermal treatment of breast cancer, the tissue is exposed to high temperatures that damage and kill cancer cells with minimal injury to normal tissues. The overall goal of our research program is to develop an image-guided, molecular specific photothermal therapy of cancer using targeted metal nanoparticles. Specifically, using targeted plasmonic nanosensors and an advanced, in-vivo, noninvasive, functional, molecular specific imaging technology (i.e., integrated ultrasound, photoacoustic and elasticity imaging), photothermal therapy can be greatly improved. Indeed, before the therapeutic procedure, using ultrasound (anatomical and blood flow imaging) and elastography (biomechanical functional imaging), the tumor will be non-invasively imaged to develop an appropriate treatment plan. Furthermore, the delivery and interaction of molecular specific photoabsorbers with cancerous tissue will be imaged using photoacoustics - a technique capable of in-vivo imaging of plasmonic nanoparticles at sufficient depth. During the therapy, the real-time imaging system will be used to guide photothermal therapy by tracking the temperature rise and, therefore, monitoring cancer treatment. Finally, after the therapy, the combined imaging will be used to accurately assess the short-term and the long-term treatment outcome. The central theme of the current application is threefold: to develop multifunctional plasmonic nanoparticles acting as both photoabsorbers for photothermal therapy and contrast agent for molecular and thermal imaging;to design and build a laboratory prototype of the integrated ultrasound, photoacoustic and elasticity imaging system;and to initially test the developed nanoparticles and imaging technology in 3-D tissue phantoms and small animal cancer model ex vivo and in vivo. Therefore, all theoretical and experimental studies will be conducted to evaluate the applicability of the molecular specific, image-guided photothermal therapy to treat cancer. At the end of the study, we will outline the design and technical specifications of a clinical image- guided photothermal therapy system.

Public Health Relevance

Cancer is a disease characterized by uncontrollable, abnormal growth of cells. The resulting tumor can invade and destroy the surrounding healthy tissue. Cancer is the second leading cause of death in the United States, exceeded only by heart disease. Breast cancer treatment often requires surgery and adjuvant therapy such as thermotherapy. In thermal treatment of breast cancer the tissue is exposed to high temperatures that damage and kill cancer cells with minimal injury to normal tissues. The primary goal of thermal treatment of cancer is to selectively heat a small volume of cancerous cells leading to tumor necrosis while protecting the surrounding healthy tissue. Thus, to successfully perform photothermal cancer therapy, an imaging technique that can help effectively plan, guide and monitor the photothermal therapy is needed. The overall goal of our research program is to develop the targeted multifunctional nanoparticles and the combined ultrasound, photoacoustic and elasticity imaging system to assist photothermal therapy. Before the therapeutic procedure, the tumor will be non-invasively imaged to develop an appropriate treatment plan. During the therapy, the real-time imaging system will be used to guide photothermal therapy by tracking the temperature rise and monitoring the cancer treatment. Finally, after the therapy, the combined imaging will be used to accurately assess the short-term and the long-term treatment outcome.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA149740-03
Application #
8267111
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Tandon, Pushpa
Project Start
2010-07-01
Project End
2015-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
3
Fiscal Year
2012
Total Cost
$308,434
Indirect Cost
$78,689
Name
University of Texas Austin
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
Luke, Geoffrey P; Emelianov, Stanislav Y (2014) Optimization of in vivo spectroscopic photoacoustic imaging by smart optical wavelength selection. Opt Lett 39:2214-7
Hannah, Alexander; Luke, Geoffrey; Wilson, Katheryne et al. (2014) Indocyanine green-loaded photoacoustic nanodroplets: dual contrast nanoconstructs for enhanced photoacoustic and ultrasound imaging. ACS Nano 8:250-9
Kim, Seungsoo; Chen, Yun-Sheng; Luke, Geoffrey P et al. (2014) In-vivo ultrasound and photoacoustic image- guided photothermal cancer therapy using silica-coated gold nanorods. IEEE Trans Ultrason Ferroelectr Freq Control 61:891-7
Qu, Min; Mehrmohammadi, Mohammad; Truby, Ryan et al. (2014) Contrast-enhanced magneto-photo-acoustic imaging in vivo using dual-contrast nanoparticles. Photoacoustics 2:55-62
Mehrmohammadi, Mohammad; Yoon, Soon Joon; Yeager, Douglas et al. (2013) Photoacoustic Imaging for Cancer Detection and Staging. Curr Mol Imaging 2:89-105
Cook, Jason R; Frey, Wolfgang; Emelianov, Stanislav (2013) Quantitative photoacoustic imaging of nanoparticles in cells and tissues. ACS Nano 7:1272-80
Luke, Geoffrey P; Bashyam, Ashvin; Homan, Kimberly A et al. (2013) Silica-coated gold nanoplates as stable photoacoustic contrast agents for sentinel lymph node imaging. Nanotechnology 24:455101
Joshi, Pratixa P; Yoon, Soon Joon; Hardin, William G et al. (2013) Conjugation of antibodies to gold nanorods through Fc portion: synthesis and molecular specific imaging. Bioconjug Chem 24:878-88
Bayer, Carolyn L; Kelvekar, Juili; Emelianov, Stanislav Y (2013) Influence of nanosecond pulsed laser irradiance on the viability of nanoparticle-loaded cells: implications for safety of contrast-enhanced photoacoustic imaging. Nanotechnology 24:465101
Chen, Yun-Sheng; Frey, Wolfgang; Walker, Charles et al. (2013) Sensitivity enhanced nanothermal sensors for photoacoustic temperature mapping. J Biophotonics 6:534-42

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