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: 10010539
• 负责人: Youbo Zhao
• 金额: $ 40万
• 依托单位: PHYSICAL SCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-06 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10010539
• 关键词: Achievement; Actinic keratosis; Algorithms; Animals; Area; Basal cell carcinoma; Biomedical Research; Cells; Clinic; Collaborations; Computer software; DNA Damage; Data; Dermatologist; Detection; Development; Dose; Evaluation; Exposure to; Feasibility Studies; Goals; Healthcare; Hospitals; Human; Institutes; International; Investigation; Lead; Light; Malignant Neoplasms; Measurement; Methods; Mus; Optics; PUVA Photochemotherapy; Patient-Focused Outcomes; Patients; Performance; Pharmacologic Substance; Phase; Photosensitization; Photosensitizing Agents; Prevention; Program Reviews; Protocols documentation; Reactive Oxygen Species; Research; Resolution; Sampling; Signal Transduction; Singlet Oxygen; Skin; Skin Cancer; Skin Carcinogenesis; Skin Carcinoma; Skin Care; Solar Energy; Specimen; Spectrum Analysis; Study Subject; Sunscreening Agents; System; Technology; Testing; The Sun; Time; Tissues; Treatment Efficacy; Treatment outcome; Work; base; cancer prevention; cancer therapy; carcinogenesis; clinical investigation; clinical practice; college; commercialization; cost; design; dosimetry; experience; experimental study; human subject; improved; in vivo; individual response; innovation; instrument; irradiation; minimally invasive; novel; phase 1 designs; physical science; pre-clinical; predicting response; professor; programs; prototype; reconstruction; skin cancer prevention; skin lesion; success; temporal measurement; tool; tumor; ultraviolet irradiation; Achievement; Actinic keratosis; Algorithms; Animals; Area; Basal cell carcinoma; Biomedical Research; Cells; Clinic; Collaborations; Computer software; DNA Damage; Data; Dermatologist; Detection; Development; Dose; Evaluation; Exposure to; Feasibility Studies; Goals; Healthcare; Hospitals; Human; Institutes; International; Investigation; Lead; Light; Malignant Neoplasms; Measurement; Methods; Mus; Optics; PUVA Photochemotherapy; Patient-Focused Outcomes; Patients; Performance; Pharmacologic Substance; Phase; Photosensitization; Photosensitizing Agents; Prevention; Program Reviews; Protocols documentation; Reactive Oxygen Species; Research; Resolution; Sampling; Signal Transduction; Singlet Oxygen; Skin; Skin Cancer; Skin Carcinogenesis; Skin Carcinoma; Skin Care; Solar Energy; Specimen; Spectrum Analysis; Study Subject; Sunscreening Agents; System; Technology; Testing; The Sun; Time; Tissues; Treatment Efficacy; Treatment outcome; Work; base; cancer prevention; cancer therapy; carcinogenesis; clinical investigation; clinical practice; college; commercialization; cost; design; dosimetry; experience; experimental study; human subject; improved; in vivo; individual response; innovation; instrument; irradiation; minimally invasive; novel; phase 1 designs; physical science; pre-clinical; predicting response; professor; programs; prototype; reconstruction; skin cancer prevention; skin lesion; success; temporal measurement; tool; tumor; ultraviolet irradiation

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.

项目摘要/摘要 皮肤癌是最常见的癌症形式。仅在美国，每年就有540万例 治疗了非黑色素瘤皮肤癌。在美国治疗皮肤癌的年度成本估计为 81亿美元。治疗和预防皮肤癌是一项重大的医疗挑战。身体的 科学公司（PSI），与达特茅斯学院和克利夫兰诊所合作，提案 开发一种新型的光学剂量测定技术，并在两个领域（即 光动力学期间光敏剂（PS）和单线氧（O2）的实时测量 治疗（PDT）和在紫外线照射下在皮肤中产生的单线O2的非侵入性定量。 这款超敏感的强大剂量计基于创新的“计算光谱”技术 以及低成本的硬件配置。我们建议证明单线O2的能力 指导PDT方案优化以改善皮肤癌治疗的剂量计，并支持 生物医学研究的重点是通过太阳能紫外线辐射了解皮肤损伤/癌变。 加速开发更有效的防晒产品的目标。 PDT是针对皮肤癌的有针对性的微创治疗选择。在PDT期间，单氧（O2）为 产生并负责细胞破坏。目前，很难，即使不是不可能的， 预测个人对PDT的反应。太阳能紫外线辐射会导致直接DNA损伤和 因此皮肤致癌。皮肤上的紫外线照射还会产生活性氧（ROS） 包括Singlet O2，这也会导致DNA损伤。但是，ROS的致癌作用 由UVA生产的不太了解，阻碍开发更有效的防晒产品 防止UVA和更长的波长。单线O2的实时量化将受益 应用程序又将导致皮肤癌疗法和预防的进步。 拟议的快速轨道计划的总体目的是开发和演示拟议的实时 Singlet O2剂量学技术。 PSI将与达特茅斯希区柯克医院和克利夫兰诊所合作 证明其在PDT和UV皮肤损伤研究中的应用。 Beiersdorf，主要制作人 皮肤护理产品的顾问将不成功。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的技术的可行性 体内（小鼠）和前体（人体皮肤）实验的小尺度。在第二阶段，原型将是 优化和改进的GEN-2原型将分配给三个机构进行独立测试 在大规模动物研究和人类患者测试有限的过程中。成功完成这些任务 将导致无创，强大的单线O2/PS剂量表，可以使研究和临床实践受益 用于治愈和预防皮肤癌。