Unprecedented nanotechnological advances in recent years hold the promise of revolutionizing many areas of medicine and biology, including cancer diagnostics and treatment. Approximately 90% of all cancer death arise from the metastasis spread of primary tumor. The circulating tumor cell (CTC) counts may be a marker of metastatic development, cancer recurrence, and therapeutic efficacy, which could be used to tailor therapy in order to improve cancer patient survival. However, it might be considered too late to treat patients and, hence, impossible to improve their survival when incurable metastases have already developed by the time of initial diagnosis with existing assays. The goal of this proposal is to develop a novel multifunctional not-toxic gold carbon nanotubes (GNTs) as super-contrast agent for in vivo real-time photoacoustic (PA) detection of CTCs, integrated with their photothermal (PT) treatment. We will pursue this goal through the following Specific Aims.
Aim 1. Develop advanced multifunctional hybrid nanoparticles and assess their capability for integrated diagnosis and therapy of cancer at the single-cell level in vitro.
Aim 2. Estimate the capability of the integrated PT/PA technique for in vivo detection and therapy of mimic CTCs labeled with GNTs in an animal model.
Aim 3. Ascertain the capability of GNTs as PT/PA contrast agents for preclinical monitoring and elimination of CTCs at different stages of tumor development.
Specific Aim 4. Determine the clinical capability of PA flow cytometry (PAFC) with novel contrast agents to monitor CTCs in the blood circulation of patients with metastatic tumors. The capability of a painless, non-invasive, PA technique for quantitative detection of CTCs in humans will be assessed in following stages: (1) assessment of healthy volunteer blood in vivo (control) and in vitro alone and spiked with cancer cell lines;and 2) assessment of cancer patient blood at different stages of disease ex vivo; and 3) assessment of cancer patient blood at different stages of disease in vivo. In the course of this study, we will obtain statistically significant data that will demonstrate this innovative technique's unprecedented capability for quantitatively detection and treatment CTCs in vitro and in vivo. The benefits to the public health of achieving this goal extend to routinely monitoring CTCs as early markers for the micrometastasis development and cancer recurrence in vivo in cancer patients, as well as to evaluating the efficacy of radiation, laser and chemotherapy.

Public Health Relevance

Unprecedented nanotechnological advances hold the promise of revolutionizing many areas of medicine and biology, including cancer diagnostics and treatment. The goal of this proposal is to develop novel nontoxic nanoparticles as supercontrast agents for in vivo laser detection and treatment of circulating tumor cells. The benefits to the public health of achieving this goal extend to the routine monitoring of circulating cells as early markers for micrometastasis development and cancer recurrence in vivo in cancer patients, as well as to the evaluation of the efficacy of radiation therapy, laser therapy, and chemotherapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB009230-04
Application #
8274736
Study Section
Special Emphasis Panel (ZRG1-MEDI-A (09))
Program Officer
Conroy, Richard
Project Start
2009-07-15
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2014-04-30
Support Year
4
Fiscal Year
2012
Total Cost
$310,455
Indirect Cost
$96,348
Name
University of Arkansas for Medical Sciences
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
122452563
City
Little Rock
State
AR
Country
United States
Zip Code
72205
Nedosekin, Dmitry A; Galanzha, Ekaterina I; Dervishi, Enkeleda et al. (2014) Super-resolution nonlinear photothermal microscopy. Small 10:135-42
Foster, Stephen R; Galanzha, Ekaterina I; Totten, Daniel C et al. (2014) Photoacoustically-guided photothermal killing of mosquitoes targeted by nanoparticles. J Biophotonics 7:465-73
Sarimollaoglu, Mustafa; Nedosekin, Dmitry A; Menyaev, Yulian A et al. (2014) Nonlinear photoacoustic signal amplification from single targets in absorption background. Photoacoustics 2:1-11
Nima, Zeid A; Mahmood, Meena; Xu, Yang et al. (2014) Circulating tumor cell identification by functionalized silver-gold nanorods with multicolor, super-enhanced SERS and photothermal resonances. Sci Rep 4:4752
Nedosekin, Dmitry A; Verkhusha, Vladislav V; Melerzanov, Alexander V et al. (2014) In vivo photoswitchable flow cytometry for direct tracking of single circulating tumor cells. Chem Biol 21:792-801
Kim, Jin-Woo; Galanzha, Ekaterina I; Zaharoff, David A et al. (2013) Nanotheranostics of circulating tumor cells, infections and other pathological features in vivo. Mol Pharm 10:813-30
Shao, Jingwei; Griffin, Robert J; Galanzha, Ekaterina I et al. (2013) Photothermal nanodrugs: potential of TNF-gold nanospheres for cancer theranostics. Sci Rep 3:1293
Nedosekin, Dmitry A; Galanzha, Ekaterina I; Ayyadevara, Srinivas et al. (2012) Photothermal confocal spectromicroscopy of multiple cellular chromophores and fluorophores. Biophys J 102:672-81
Nedosekin, Dmitry A; Khodakovskaya, Mariya V; Biris, Alexandru S et al. (2011) In vivo plant flow cytometry: a first proof-of-concept. Cytometry A 79:855-65
Khodakovskaya, Mariya V; de Silva, Kanishka; Nedosekin, Dmitry A et al. (2011) Complex genetic, photothermal, and photoacoustic analysis of nanoparticle-plant interactions. Proc Natl Acad Sci U S A 108:1028-33

Showing the most recent 10 out of 26 publications