Metal Organic Frameworks-Based Next-Generation Sunscreens for Cancer Prevention

基于金属有机框架的下一代癌症预防防晒霜

• 批准号: 10082046
• 负责人: R. OSMAN K. OZDEMIR
• 金额: $ 38.46万
• 依托单位: FRAMERGY, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-12 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10082046
• 关键词: 3-Dimensional; Active Sites; Address; Adsorption; Animals; Applications Grants; Area; Biological; Biological Assay; Cell model; Cells; Climacteric; Collaborations; Coupled; DNA; DNA Damage; Dermal; Development; Doctor of Philosophy; Exposure to; Female; Fibroblasts; Formulation; Free Radicals; Goals; Human; Image; Immunosuppression; Institutes; Ligands; Light; Link; Malignant Neoplasms; Mass Fragmentography; Measurement; Measures; Medicine; Melanins; Melanoma Cell; Metals; Modeling; Nanostructures; Nanotechnology; National Cancer Institute; Oxides; Particle Size; Performance; Peroxides; Phase; Photobiology; Photochemistry; Prevention; Production; Reactive Oxygen Species; Research; Role; Skin; Skin Aging; Skin Cancer; Solar Energy; Squamous cell carcinoma; Sunburn; Sunscreening Agents; Surface; Technology; Testing; Texas; The Sun; Titanium; UV Radiation Exposure; UV induced; UV protection; UV-induced melanoma; Ultraviolet Rays; Universities; Visible Radiation; Water; absorption; analytical method; base; cancer prevention; college; commercialization; cytotoxicity; effectiveness measure; experimental study; improved; innovation; irradiation; keratinocyte; male; melanoma; next generation; novel; preclinical study; preclinical trial; premature; prevent; product development; skin cancer prevention; skin patch; stability testing; technology development; titanium dioxide; ultraviolet; ultraviolet irradiation

Project Summary/Abstract In this grant application, framergy, in collaboration with Baylor College of Medicine, will demonstrate a promising next- generation skin cancer prevention technology, with the ultimate goal being successful commercialization and life-changing public benefit. The team will utilize a novel class of nanostructured material, called Metal-organic Frameworks (MOFs), to prevent ultraviolet (UV)-induced melanoma and squamous cell carcinomas by blocking UV light and absorbing cancer triggering, byproduct free-radicals on the skin. Studies have shown that exposure to solar radiation (UV/Visible radiation) from the sun results in sunburn and has been linked to premature skin aging, immunosuppression and skin cancer. The number of new cases of melanoma has been increasing for at least 30 years. Sunscreen may help decrease the amount of UV radiation to the skin. According to National Cancer Institute, wearing sunscreen can help prevent actinic keratoses, scaly patches of skin that sometimes- become squamous cell carcinoma. Despite increased use of sunscreens over the years, skin cancer rates have continued to rise. There are two impediments to the development of next generation sunscreens: 1) The insufficient magnitude of UV protection of current products on the market, including strong inorganic UV protectors like TiO2 and ZnO, and 2) the fact that these inorganic protectors generate reactive oxygen species (ROS) which combine with organic compounds in the formula, or on the skin, to form harmful byproducts. Recent advances in porous coordination network materials, such as MOFs, can address the need for improved breadth and magnitude of UV protection while capturing the toxic reactive oxygen species and radical byproducts generated under solar radiation. During Phase I, framergy will down-select the optimal titanium MOF for the composition through UV absorbance testing, heat of adsorption testing, water stability testing and controlled particle size synthesis. Further, framergy will take a top down and bottom up approach to demonstrate the performance of organic peroxide scavenging of the MOF. Baylor College of Medicine will assist this technology development activity by performing biological experiments in 2D cell models measuring the effects of UV irradiation on DNA damage and ROS production, with and without the application of MOFs. These assays will be imaging-based, medium and high throughput automated experiments coupled with single cell analytics. This will help shed light on the role of MOFs in the prevention of UV induced melanomas. Testing MOFs in 3D skin models across Phase I and II will further strengthen results ahead of preclinical studies. In the Phase II period, framergy and the BCM team will collaborate with Texas Institute for Preclinical Studies (Texas A&M University) to conduct preclinical trials to conduct cytotoxicity and photogenotoxicity studies to transition the product development activities from cell-level to large animal preclinical trials.

项目总结/摘要 在这次拨款申请中，framergy与贝勒医学院合作，将展示一个有前途的下一个- 新一代皮肤癌预防技术，最终目标是成功商业化和改变生活 公共利益。该团队将利用一种新型的纳米结构材料，称为金属有机框架（MOFs）， 通过阻挡紫外线和吸收癌症，预防紫外线（UV）诱导的黑色素瘤和鳞状细胞癌 引发皮肤上的副产品自由基 研究表明，暴露于来自太阳的太阳辐射（紫外线/可见光辐射）导致晒伤，并且已经被 与皮肤过早老化免疫抑制和皮肤癌有关黑色素瘤的新病例数 增长至少30年。防晒霜可以帮助减少对皮肤的紫外线辐射量。根据 美国国家癌症研究所，涂防晒霜可以帮助防止光化性角化病，鳞状皮肤补丁，有时- 变成鳞状细胞癌 尽管近年来防晒霜的使用越来越多，但皮肤癌的发病率仍在继续上升。有两个障碍 下一代防晒霜的发展：1）目前产品的紫外线防护程度不足， 市场，包括强无机UV保护剂如TiO 2和ZnO，以及2）这些无机保护剂 产生活性氧物质（ROS），其与配方中或皮肤上的有机化合物联合收割机结合， 有害 副产品多孔配位网络材料（例如MOF）的最新进展可以满足以下需求 提高紫外线防护的广度和强度，同时捕获有毒的活性氧物质和自由基 在太阳辐射下产生的副产品。 在第一阶段，framergy将通过紫外吸收测试为组合物选择最佳的钛MOF， 吸附热测试、水稳定性测试和受控粒度合成。此外，框架将占据榜首 自下而上和自下而上的方法来证明MOF的有机过氧化物清除性能。贝勒 医学院将通过在2D细胞模型中进行生物实验来协助这项技术开发活动 测量UV照射对DNA损伤和ROS产生的影响，有和没有应用MOF。 这些试验将是基于成像的中、高通量自动化实验，结合单细胞免疫分析。 分析学这将有助于阐明MOFs在预防紫外线诱导的黑色素瘤中的作用。在3D中测试MOF I期和II期的皮肤模型将进一步加强临床前研究的结果。 在第二阶段，framergy和technology团队将与德克萨斯临床前研究所（Texas A&M）合作 大学）进行临床前试验，以进行细胞毒性和光遗传毒性研究，从而将产品 从细胞水平到大型动物临床前试验的开发活动。