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

用于皮肤癌治疗和预防的超灵敏单线态氧剂量计

• 批准号: 10425539
• 负责人: Youbo Zhao
• 金额: $ 92.62万
• 依托单位: PHYSICAL SCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10425539
• 关键词: Ultra; sensitive; Singlet; Oxygen; Dosimeter

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.

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 非黑色素瘤皮肤癌得到治疗。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。身体的 Sciences Inc. (PSI) 与达特茅斯学院和克利夫兰诊所合作，提议 开发一种新型光学剂量测定技术并展示其在两个领域的应用，即 光动力过程中光敏剂（PS）和单线态氧（O2）的实时测量 疗法（PDT），以及紫外线照射下皮肤产生的单线态 O2 的无创定量。 这种超灵敏、坚固的剂量计基于创新的“计算光谱”技术 以及低成本的硬件配置。我们建议展示单线态 O2 的能力 剂量计可指导优化 PDT 方案以改善皮肤癌治疗，并支持 生物医学研究的重点是了解太阳紫外线照射造成的皮肤损伤/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 期间，单线态氧 (O2) 产生并负责细胞破坏。目前，即使不是不可能，也是困难的 预测个体对 PDT 的反应。太阳紫外线照射会导致 DNA 直接损伤 从而导致皮肤癌变。皮肤上的紫外线照射也会产生活性氧 (ROS) 包括单线态 O2，它也会导致 DNA 损伤。然而，ROS的致癌作用 UVA产生的物质尚不清楚，阻碍了开发更有效的防晒产品 防止 UVA 和更长波长的伤害。单线态 O2 的实时定量将使双方受益 应用，反过来又将促进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 展示其在 PDT 和紫外线皮肤损伤研究中的应用。拜尔斯多夫 (Beiersdorf)，主要生产商 的护肤品将作为顾问免费参与该计划。第一阶段将重点关注 通过开发两个原型并对其进行测试来证明所提出技术的可行性 小规模体内（小鼠）和离体（人类皮肤）实验。在第二阶段，原型将 优化和改进的Gen-2原型机将分发给三个机构进行独立测试 在大规模动物研究和有限的人类患者测试中。顺利完成这些任务 将产生一种无创、稳健的单态 O2/PS 剂量计，有利于研究和临床实践 用于治疗和预防皮肤癌。