The thermal ablation of tumors, encompassing laser ablation and focused ultrasound and radiofrequency ablation, is an alternative method to overcome the problems associated with open surgery and is founded on destruction of tumors by applying the heat directly to the tumor site. Thermal treatment of tumors, however, is hindered if the tumor is in close proximity to vital organs sensitive to overheating. On the other hand, over-cautious heating results in incomplete tumor eradication and early tumor recurrences. Therefore, control over the heating process is of critical importance to ensure uniform and adequate heating of the tumor. The development of an optically guided method to control and improve thermal ablation constitutes the overall goal of this project. We propose a method of tumor treatment based on thermal ablation enhanced with temperature sensitive nanoparticles (nanothermometers). The principle of temperature sensitivity of the nanothermometers is based on thermally induced fluorescence. At a normal body temperature, the nanoparticles are invisible;upon heating, the nanoparticles generate fluorescence and become visible. Towards our goal, we will synthesize different nanoparticles and optimize their properties. The temperature sensitive nanoparticles will be constructed from non-toxic materials such as gold, near infrared dyes frequently used in diagnostics, and linkers composed from common amino acids or polyethylene glycols. The nanoparticles will be rigorously tested in vitro, in cells, phantoms and in small animals. In the conclusion of the study, the nanoparticles will be delivered to the tumor site and the tumor will be exposed to the thermal energy. We will be using laser ablation as a method of choice for delivering thermal energy. Under laser ablation conditions, the proposed nanoparticles will provide three important functions: i they will report and control the heating process by turning fluorescence """"""""ON"""""""" at the desired temperature, ii they will convert light energy to heat, increasing the temperature inside the tumor, and iii they will propagate energy deep into the tumor, thus providing uniform heating. We expect to establish a strong foundation for utilizing thermal ablation in combination with temperature sensitive nanoparticles in the treatment of tumors. The development of such novel biomedical technology would represent a significant advancement in the treatment of cancer.

Public Health Relevance

The goal of this project is to develop an optically guided thermal ablation method for treatment of tumors using nanothermometers to ensure both uniform and adequate heating of the tumors. These nanothermometers will allow for a higher level of control over the ablation procedure and render the treatment of tumors safer by lowering the chances of tumor recurrences.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA149814-02
Application #
8054330
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Tandon, Pushpa
Project Start
2010-04-01
Project End
2013-03-31
Budget Start
2011-04-01
Budget End
2013-03-31
Support Year
2
Fiscal Year
2011
Total Cost
$160,342
Indirect Cost
Name
Washington University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Cheadle, Carl; Ratcliff, Jessica; Berezin, Mikhail et al. (2017) Shortwave infrared luminescent Pt-nanowires: a mechanistic study of emission in solution and in the solid state. Dalton Trans 46:13562-13581
Klaus, Danielle R; Keene, Matthew; Silchenko, Svitlana et al. (2015) 1D polymeric platinum cyanoximate: a strategy toward luminescence in the near-infrared region beyond 1000 nm. Inorg Chem 54:1890-900
Zhegalova, Natalia G; He, Shawn; Zhou, Haiying et al. (2014) Minimization of self-quenching fluorescence on dyes conjugated to biomolecules with multiple labeling sites via asymmetrically charged NIR fluorophores. Contrast Media Mol Imaging 9:355-62
Zhegalova, Natalia G; Dergunov, Sergey A; Wang, Steven T et al. (2014) Design of fluorescent nanocapsules as ratiometric nanothermometers. Chemistry 20:10292-7
Zhegalova, Natalia G; Gonzales, Garrett; Berezin, Mikhail Y (2013) Synthesis of nitric oxide probes with fluorescence lifetime sensitivity. Org Biomol Chem 11:8228-34
Wang, Steven T; Zhegalova, Natalia G; Gustafson, Tiffany P et al. (2013) Sensitivity of activatable reactive oxygen species probes by fluorescence spectroelectrochemistry. Analyst 138:4363-9
Magalotti, Selena; Gustafson, Tiffany P; Cao, Qian et al. (2013) Evaluation of inflammatory response to acute ischemia using near-infrared fluorescent reactive oxygen sensors. Mol Imaging Biol 15:423-30
Gustafson, Tiffany P; Dergunov, Sergey A; Akers, Walter J et al. (2013) BLOOD TRIGGERED RAPID RELEASE POROUS NANOCAPSULES. RSC Adv 3:5547-5555
Gustafson, Tiffany P; Cao, Qian; Wang, Steven T et al. (2013) Design of irreversible optical nanothermometers for thermal ablations. Chem Commun (Camb) 49:680-2
Cao, Qian; Zhegalova, Natalia G; Wang, Steven T et al. (2013) Multispectral imaging in the extended near-infrared window based on endogenous chromophores. J Biomed Opt 18:101318

Showing the most recent 10 out of 14 publications