Ultra-sensitive Singlet Oxygen Dosimeter for Skin Cancer Treatment and Prevention

项目摘要/摘要 皮肤癌是最常见的癌症形式。仅在美国，每年就有超过540万起 治疗非黑色素瘤皮肤癌。在美国，每年治疗皮肤癌的费用估计为 81亿美元。皮肤癌的治疗和预防是一项重大的卫生保健挑战。物理 Science Inc.(PSI)与达特茅斯学院和克利夫兰诊所合作，提议 开发一种新的光学剂量测量技术，并展示其在两个领域的应用，即， 光动力学过程中光敏剂(PS)和单线态氧(O2)的实时测量 光动力疗法(PDT)，以及紫外线照射下皮肤产生的单线态氧的无创定量。 这种超灵敏、坚固耐用的剂量计基于一种创新的“计算光谱学”技术。 和低成本的硬件配置。我们建议演示单线态O2的能力 剂量计，用于指导优化PDT方案以改进皮肤癌治疗，以及支持 生物医学研究的重点是了解太阳紫外线辐射对皮肤的损害/致癌作用 加速开发更有效的防晒产品的目标。 PDT是皮肤癌的一种有针对性的微创治疗选择。在PDT过程中，单线态氧(O2)是 产生并对细胞的破坏负责。目前，这是困难的，如果不是不可能的话， 以预测个体对光动力疗法的反应。太阳紫外线辐射会导致DNA直接损伤和 因此，皮肤癌的发生。紫外线照射皮肤也会产生活性氧(ROS)。 包括单线态O2，这也会导致DNA损伤。然而，ROS的致癌作用 UVA生产的防晒霜不被很好地理解，阻碍了更有效的防晒产品的开发 可以抵御UVA和更长波长的紫外线。实时量化单线态氧对双方都有好处 应用，这反过来将导致皮肤癌治疗和预防的进步。 建议的Fast Track计划的总体目标是开发和演示建议的实时 单线态氧剂量测量技术。PSI将与达特茅斯希区柯克医院和克利夫兰诊所合作 展示了它在光动力疗法和紫外线皮肤损伤调查中的应用。主要生产商拜尔斯多夫 护肤品的一部分将以顾问的身份参加，该计划不收取任何费用。第一阶段将重点放在 通过开发两个原型并在其上进行测试，证明了所建议技术的可行性 小规模的体内(小鼠)和体外(人体皮肤)实验。在第二阶段，原型将是 优化和改进的第二代原型将分发给三个研究所进行独立测试 在大规模的动物研究和有限的人类患者测试中。圆满完成这些任务 将导致一种非侵入性、坚固耐用的单重态O2/PS剂量计，这将有助于研究和临床实践 用于治疗和预防皮肤癌。

Project Summary/Abstract Skin cancer is the most common form of cancer. Each year in the U.S. alone over 5.4 million cases of nonmelanoma skin cancer are treated. The annual cost of treating skin cancers in the U.S. is estimated at $8.1 billion. Treatment and prevention of skin cancer is a significant health care challenge. Physical Sciences Inc. (PSI), in collaboration with Dartmouth College and Cleveland Clinic, proposes to develop a novel optical dosimetry technology and demonstrate its applications in two areas, i.e., real-time measurement of photosensitizer (PS) and singlet oxygen (O2) during photodynamic therapy (PDT), and non-invasive quantification of singlet O2 produced in skin under UV irradiation. This ultrasensitive, robust dosimeter is based on an innovative “computational spectroscopy” technology and a low-cost hardware configuration. We propose to demonstrate the capability of the singlet O2 dosimeter to guide optimization of PDT protocols for improved skin cancer treatment, as well as to support biomedical research focused on understanding skin damage/carcinogenesis by solar UV irradiation with a goal of accelerating the development of more effective sunscreen products. PDT is a targeted, minimally invasive treatment option for skin cancer. During PDT, singlet oxygen (O2) is produced and is responsible for the cell destruction. At the present time it is difficult, if not impossible, to predict the response of an individual to PDT. Solar UV irradiation causes direct DNA damage and thus skin carcinogenesis. UV irradiation on the skin also generates reactive oxygen species (ROS) including singlet O2, which also contributes to DNA damage. However, the carcinogenesis of ROS produced by UVA is not well understood, hindering developing more effective sunscreen products that protect against UVA and longer wavelengths. Real-time quantification of singlet O2 will benefit both applications, which, in turn, will lead to advancements in skin cancer therapy and prevention. The overall aim of the proposed Fast Track program is to develop and demonstrate the proposed real-time singlet O2 dosimetry technology. PSI will work with Dartmouth Hitchcock Hospital and Cleveland Clinic to demonstrate its application in both PDT and UV skin damage investigations. Beiersdorf, a major producer of skin care products will participate as a consultant at no cost to the program. Phase I will focus on demonstrating the feasibility of the proposed technology, by developing two prototypes and testing them on small scale in vivo (mice) and ex-vivo (human skin) experiments. During Phase II, the prototypes will be optimized and the improved Gen-2 prototypes will be distributed to three institutes for independent testing during large-scale animal studies and limited human patient testing. Successful completion of these tasks will lead to a noninvasive, robust singlet O2/PS dosimeter that could benefit research and clinical practice for curing and preventing skin cancer.