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

项目摘要/摘要 在这项拨款申请中，Framergy与贝勒医学院合作，将展示一种有前途的下一步- 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。该团队将利用一种名为金属有机骨架(MOF)的新型纳米结构材料来 通过阻断紫外线和吸收癌症来预防紫外线诱导的黑色素瘤和鳞状细胞癌 触发皮肤上的副产品自由基。 研究表明，暴露在太阳辐射(紫外线/可见光辐射)下会导致晒伤，并已被 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量一直是 至少增长了30年。防晒霜可能有助于减少对皮肤的紫外线辐射量。根据 美国国家癌症研究所称，涂抹防晒霜有助于预防光化性角化病，即皮肤鳞片，有时- 变成鳞状细胞癌。 尽管多年来防晒霜的使用量有所增加，但皮肤癌的发病率仍在继续上升。有两个障碍 对下一代防晒霜的发展：1)现有产品对紫外线的防护力度不足 市场上，包括强大的无机紫外线保护剂，如二氧化钛和氧化锌，和2)事实是，这些无机保护剂 产生活性氧物种(ROS)，它与配方中的有机化合物结合，或在皮肤上形成 有害 副产品。多孔性配位网络材料的最新进展，如MOF，可以满足以下需求 提高了紫外线防护的广度和幅度，同时捕获有毒的活性氧物种和自由基 在太阳辐射下产生的副产品。 在第一阶段，Framergy将通过紫外线吸收测试为组合物下选择最佳的钛MOF， 吸附热测试、水稳定性测试和可控粒度合成。此外，Framergy将获得一个顶部 向下和自下而上的方法来展示MOF对有机过氧化氢的清除性能。贝勒 医学院将通过在2D细胞模型中进行生物学实验来协助这项技术开发活动 测量紫外线照射对DNA损伤和ROS产生的影响，使用和不使用MOF的情况下。 这些分析将是基于成像的、中高通量的自动化实验，与单细胞相结合 分析。这将有助于阐明MOF在预防紫外线诱导的黑色素瘤中的作用。在3D模式下测试MOF 第一阶段和第二阶段的皮肤模型将在临床前研究之前进一步加强结果。 在第二阶段，Framergy和BCM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，以过渡产品 从细胞水平到大型动物临床前试验的开发活动。

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.