A novel antioxidant delivery system, Pro-NP™, for protection against UV-related skin cancer

一种新型抗氧化剂输送系统 Pro-NP™，可预防与紫外线相关的皮肤癌

• 批准号: 10258423
• 负责人: Gary Leonard Madsen
• 金额: $ 26.12万
• 依托单位: PROTRANSIT NANOTHERAPY, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10258423
• 关键词: Affect; American; Antioxidants; Biological; Case Study; Catalysis; Collagen; Collagen Fiber; Cutaneous; DNA Damage; Data; Defense Mechanisms; Dermatologic; Development; Dose; Drug Delivery Systems; Ear; Elastin; Elastin Fiber; Enzymes; Epidermis; Event; Excision; Exposure to; Family suidae; Fiber; Formulation; Gene Mutation; Generations; Goals; Half-Life; Hour; Human; Human Volunteers; Incidence; Inflammation; Ions; Lipid Peroxidation; Malignant Neoplasms; Modeling; Mus; Nanotechnology; Oncogenic; Oxidative Stress; Plants; Polymers; Prevention; Production; Proteins; Reactive Inhibition; Reactive Oxygen Species; Risk; Signal Pathway; Skin; Skin Cancer; Skin Care; Skin Neoplasms; Sun Exposure; Sunscreening Agents; Superoxide Dismutase; System; Therapeutic; Topical application; UV Radiation Exposure; UV induced; UV induced DNA damage; Ultraviolet Rays; United States; Vitamins; antioxidant enzyme; base; catalase; cell injury; combat; comparative efficacy; compare effectiveness; innovation; keratinocyte; metal chelator; nanoformulation; nanoparticle; nanoparticle drug; next generation; novel; oxidative damage; prevent; skin damage; skin organogenesis; tanning booths; titanium dioxide; tumorigenesis; ultraviolet

ABSTRACT This project aims to develop a skincare product to prevent ultraviolet (UV)-induced skin cancer with a novel antioxidant delivery system, Pro-NP™, for topical application alone or as an additive to commercial sunblock. Skin cancer is more common than all other cancers combined and affects millions of Americans every year. UV exposure from the sun or tanning beds causes the production of reactive oxygen species (ROS), which overwhelms the skin’s natural antioxidant defense and leads to oxidative stress, photoaging, and skin cancer. While commercial sunscreens can reduce the risk of developing skin cancer, they are poor at blocking UV-A rays responsible for most of the cutaneous ROS production. The topical application of exogenous antioxidants could potentially combat UV generated ROS; however, in their native state, many antioxidants are too unstable to absorb to the deeper layers of the skin effectively. The natural defense system of the skin against UV-induced oxidative stress includes antioxidants superoxide dismutase (SOD) and catalase (CAT), essential enzymes that neutralize the detrimental effects of ROS. Unfortunately, the catalytic activity of native SOD and CAT are short- lived and rapidly cleared, a limiting factor on current therapeutic strategies based on exogenous delivery. ProTransit has developed a proprietary antioxidant delivery system, Pro-NP™, specially formulated for the slow- sustained release of SOD and CAT, to overcome the limitation of the antioxidant’s short half-life. The development of our dermatological product capitalizes on the recent advances of nanotechnology to overcome the biological barriers of using antioxidants to counteract skin damage caused by ROS. Our preliminary studies are promising and demonstrate that Pro-NP is non-toxic in humans and penetrates to the deepest layers of the skin to release active SOD and CAT, reduces DNA damage after UV exposure, and prevents the degradation of essential skin protein fibers like elastin and collagen. The overall objective of this study is to optimize the formulation of plant-based SOD and CAT in Pro-NP, determine the window of efficacy, compare the effectiveness of Pro-NP to commercially available sunscreens, and evaluate the potential of co-application of Pro-NP with commercial sunscreens. Our long-term goal is to develop novel, next-generation skincare products for topical application to prevent UV-induced skin damage and ultimately to reduce the incidence of skin cancer.

抽象的 该项目旨在开发一种护肤产品，通过一种新颖的成分来预防紫外线 (UV) 诱发的皮肤癌 抗氧化剂输送系统 Pro-NP™，可单独局部使用或作为商业防晒霜的添加剂。 皮肤癌比所有其他癌症加起来更常见，每年影响数百万美国人。 暴露于阳光或晒黑床会导致活性氧 (ROS) 的产生， 破坏皮肤的天然抗氧化防御能力，导致氧化应激、光老化和皮肤癌。 虽然商业防晒霜可以降低患皮肤癌的风险，但它们在阻挡 UV-A 方面效果不佳 射线负责大部分皮肤活性氧的产生 外源性抗氧化剂的局部应用。 可能会对抗紫外线产生的活性氧；然而，在其天然状态下，许多抗氧化剂都太不稳定 有效吸收到皮肤深层，皮肤抵御紫外线的天然防御系统。 氧化应激包括抗氧化剂超氧化物歧化酶 (SOD) 和过氧化氢酶 (CAT)，这些酶是 不幸的是，天然 SOD 和 CAT 的催化活性很短。 存活并迅速清除，这是当前基于外源性递送的治疗策略的限制因素。 ProTransit 开发了一种专有的抗氧化剂输送系统 Pro-NP™，专门针对慢速 持续释放SOD和CAT，克服抗氧化剂半衰期短的限制。 我们的皮肤科产品的开发利用了纳米技术的最新进展来克服 我们的初步研究使用抗氧化剂来抵消 ROS 引起的皮肤损伤的生物屏障。 前景广阔，并证明 Pro-NP 对人体无毒，并能渗透到人体最深层 皮肤释放活性SOD和CAT，减少紫外线照射后DNA损伤，防止降解 这项研究的总体目标是优化皮肤必需的蛋白质纤维，如弹性蛋白和胶原蛋白。 Pro-NP 中植物基 SOD 和 CAT 的配方，确定功效窗口，比较 Pro-NP 对市售防晒霜的有效性，并评估共同应用的潜力 Pro-NP 与商业防晒霜我们的长期目标是开发新颖的下一代护肤品。 局部应用产品可防止紫外线引起的皮肤损伤，并最终减少皮肤病的发生 皮肤癌。