DEVELOPMENT OF OPTICAL NANOTHERMOMETERS FOR MEDICAL APPLICATIONS

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DESCRIPTION (provided by applicant): 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.