STTR Phase I: Monobenzone (MBEH) Supercarriers: Production and Melanoma Treatment

这个小企业技术转让（STTR）第一阶段项目开发了一种新的具有成本效益的黑色素瘤治疗方法，可以在家中和偏远地区进行治疗。该项目的重要性反映在每年有10万人被诊断患有这种毁灭性的皮肤癌，以及每年有8,000名患者死于这种疾病。概念验证是朝着开发治疗III期和IV期黑色素瘤的新疗法迈出的一步。总体目标是在组织和细胞水平上开发手术精确的药物递送，这将导致组织水平触发免疫反应，从而增强药物的影响。 与竞争性治疗方案相比，该解决方案应大幅减少副作用。该方法允许现成的交付，使生活在偏远地区的患者能够获得最先进的治疗。美国每年用于黑色素瘤治疗的费用为57亿美元。针对III期和IV期疾病的药物占15亿美元（26%）。这个小企业技术转让（STTR）项目旨在展示治疗III期和IV期黑色素瘤的超级载体的概念验证。该申请采用月桂酰-莫诺苯宗产生选择性抗黑色素瘤作用和有效的免疫激活，将药物包装在生物相容性纳米级脂质体颗粒中用于选择性黑色素瘤递送。该设计通过将活性成分直接输送到肿瘤来增强功效，同时最大限度地减少副作用。由于肿瘤细胞而不是健康组织选择性地摄取纳米颗粒，并且由于超载体内容物仅在纳米颗粒进入溶酶体/黑素体区室时释放，因此影响将主要（如果不是排他的话）由肿瘤感受。酪氨酸酶将前药转化为醌，醌使存在的黑素体酶半抗原化以产生对T细胞具有增加的可见性的新抗原。由此产生的直接和间接黑色素瘤细胞毒性形成了超级载体治疗成功的关键。低毒性，结合简单的现成交付，提高患者的生活质量。由于增强的免疫活性没有针对患者的定制，因此该应用程序允许方便和有吸引力的成本质量比。灵活、近距离给药、副作用少、成本低和预期寿命延长有望建立药物的声誉，推动需求。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This Small Business Technology Transfer (STTR) Phase I project develops a novel cost-effective treatment for melanoma that allows treatment delivery both at home and in remote geographic locations. The importance of the project is reflected in the 100,000 individuals that are diagnosed with this devastating skin cancer annually as well as by 8,000 patients a year being lost to the disease. The proof of concept is a step towards the development of a novel therapy for the treatment of stage III and IV melanoma. The overarching goal is to develop surgically accurate drug delivery at both the tissue and cellular levels that will result in a tissue-level triggering of an immune response that heightens the impact of the drug. The solution should drastically decreased side effects when compared to competing treatment alternatives. The method allows for off-the-shelf delivery, giving patients living in remote locations access to state-of-the-art therapy. Annually, $5.7 billion is spent on melanoma treatment in the US. Drugs targeting stage III and IV disease make up $1.5 billion (26%). This Small Business Technology Transfer (STTR) project aims to demonstrate proof of concept for supercarriers that will treat stage III and IV melanomas. The application employs lauroyl-monobenzone to produce selective anti-melanoma action and effective immune activation, packaging the drug in biocompatible nanoscale liposomal particles for selective melanoma delivery. The design enhances efficacy while minimizing side effects by transporting the active ingredient directly to the tumor. Due to the selective uptake of nanoparticles by tumor cells rather than healthy tissues, and because supercarrier contents are released only when the nanoparticles enter the lysosomal/melanosomal compartment, the impact will be felt primarily, if not exclusively, by the tumor. Tyrosinase converts the prodrug into a quinone that haptenizes the melanosomal enzyme(s) present to generate neoantigens with increased visibility for T cells. The resulting direct and indirect melanoma cytotoxicity form the key to supercarrier treatment success. Low toxicity, combined with simple off-the-shelf delivery, enhance patient quality of life. As enhanced immune activity comes without patient-specific tailoring, the application allows for convenience and an attractive cost-to-quality ratio. Flexible, close-to-home drug delivery, few side effects, low cost, and enhanced life expectancy are expected to build the reputation of the drug, propelling the demand.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.