DEVELOPMENT OF OPTICAL NANOTHERMOMETERS FOR MEDICAL APPLICATIONS

描述（由申请人提供）：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一种替代方法，其基础是通过直接对肿瘤部位施加热量来破坏肿瘤。然而，如果肿瘤靠近对过热敏感的重要器官，则会阻碍肿瘤的热治疗。另一方面，过于谨慎的加热导致肿瘤不完全根除和早期肿瘤复发。因此，控制加热过程对于保证肿瘤的均匀和充分加热至关重要。开发一种光学引导方法来控制和改善热烧蚀是本项目的总体目标。我们提出了一种基于温度敏感纳米颗粒（纳米温度计）增强热消融的肿瘤治疗方法。纳米温度计的温度敏感性原理是基于热诱导荧光。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变得可见。为了实现我们的目标，我们将合成不同的纳米颗粒并优化它们的性能。这种对温度敏感的纳米粒子将由无毒材料制成，比如金、常用于诊断的近红外染料，以及由普通氨基酸或聚乙二醇组成的连接剂。这些纳米粒子将在体外、细胞、幻影和小动物身上进行严格的测试。在研究的最后，纳米颗粒将被递送到肿瘤部位，肿瘤将暴露在热能中。我们将使用激光烧蚀作为传递热能的一种方法。在激光消融条件下，所提出的纳米颗粒将提供三个重要功能：一是通过在所需温度下将荧光“打开”来报告和控制加热过程；二是将光能转化为热能，提高肿瘤内部的温度；三是将能量传播到肿瘤深处，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颗粒治疗肿瘤奠定坚实的基础。这种新型生物医学技术的发展将代表癌症治疗的重大进步。

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.