DEVELOPMENT OF OPTICAL NANOTHERMOMETERS FOR MEDICAL APPLICATIONS

描述(申请人提供)：肿瘤的热消融，包括激光消融、聚焦超声和射频消融，是克服开放手术相关问题的另一种方法，其基础是通过将热直接施加到肿瘤部位来破坏肿瘤。然而，如果肿瘤靠近对过热敏感的重要器官，那么肿瘤的热疗就会受到阻碍。另一方面，过度谨慎的加热会导致肿瘤清除不彻底和肿瘤早期复发。因此，对加热过程的控制对于确保肿瘤的均匀和足够的加热至关重要。开发一种控制和改善热烧蚀的光学制导方法是该项目的总体目标。我们提出了一种基于温度敏感纳米颗粒(纳米温度计)增强的热消融治疗肿瘤的方法。纳米温度计的温度灵敏度原理是基于热诱导荧光的。在正常体温下，纳米颗粒是看不见的；加热后，纳米颗粒产生荧光并可见。朝着我们的目标，我们将合成不同的纳米颗粒，并优化它们的性能。温度敏感的纳米颗粒将由无毒材料构建，如金，经常用于诊断的近红外染料，以及由常见氨基酸或聚乙二醇组成为连接物。这些纳米粒子将在体外、细胞、幻影和小动物中进行严格的测试。在研究的结论中，纳米颗粒将被输送到肿瘤部位，肿瘤将暴露在热能中。我们将使用激光消融作为输送热能的一种选择方法。在激光消融条件下，提出的纳米粒子将提供三个重要功能：i它们将报告和控制加热过程，在所需的温度下打开荧光；ii它们将光能转换为热，从而提高肿瘤内部的温度；iii它们将能量传播到肿瘤的深处，从而提供均匀的加热。我们期望为利用热消融结合温度敏感纳米粒子治疗肿瘤奠定坚实的基础。这种新的生物医学技术的发展将代表着癌症治疗方面的重大进步。 与公共卫生相关：该项目的目标是开发一种使用纳米温度计的光学引导热消融治疗肿瘤的方法，以确保肿瘤的均匀和足够的加热。这些纳米温度计将允许对消融过程进行更高水平的控制，并通过降低肿瘤复发的机会使肿瘤治疗更加安全。

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.