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

项目概要/摘要 皮肤癌是最常见的癌症形式。仅在美国，每年就有超过540万例 非黑色素瘤皮肤癌的治疗。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 Sciences Inc. (PSI)与达特茅斯学院和克利夫兰诊所合作，建议 发展一种新的光学剂量测定技术，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），以及在紫外线照射下皮肤中产生的单线态O2的非侵入性定量。 这种超灵敏、坚固的剂量计基于创新的“计算光谱学”技术 和低成本的硬件配置。我们建议证明单线态O2的能力 剂量计，以指导优化PDT方案，改善皮肤癌治疗，以及支持 生物医学研究侧重于了解太阳紫外线照射引起的皮肤损伤/致癌作用， 目标是加速开发更有效的防晒产品。 PDT是皮肤癌的靶向微创治疗选择。在PDT过程中，单线态氧（O2） 产生并负责细胞的破坏。目前，如果不是不可能的话， 来预测个体对PDT的反应。太阳紫外线照射导致DNA直接损伤， 从而导致皮肤癌变。紫外线照射皮肤也会产生活性氧（ROS） 包括单线态O2，它也会导致DNA损伤。然而，ROS的致癌作用 人们对UVA产生的紫外线还不太了解，这阻碍了开发更有效的防晒产品。 可以抵御UVA和更长波长的紫外线。单线态O2的实时定量将使两者受益 这反过来将导致皮肤癌治疗和预防的进步。 拟议的快速通道计划的总体目标是开发和演示拟议的实时 单线态O2剂量测定技术。PSI将与达特茅斯希区柯克医院和克利夫兰诊所合作， 展示了其在PDT和UV皮肤损伤研究中的应用。拜尔斯多夫，一个主要的生产商 护肤品的销售商将作为顾问参加该计划，不收取任何费用。第一阶段将侧重于 通过开发两个原型并在 小规模体内（小鼠）和离体（人皮肤）实验。在第二阶段，原型将 经过优化和改进的第二代原型机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 将导致一个非侵入性的，强大的单线态O2/PS剂量计，可能有利于研究和临床实践 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.