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

这个小型企业技术转移(STTR)第一阶段项目开发了一种新的治疗黑色素瘤的经济高效的方法，可以在家里和偏远的地理位置提供治疗。该项目的重要性反映在每年有10万人被诊断出患有这种毁灭性的皮肤癌，以及每年有8000名患者死于这种疾病。这一概念验证是朝着开发一种治疗III和IV期黑色素瘤的新疗法迈出的一步。首要目标是在组织和细胞水平上开发外科准确的药物输送，这将导致组织水平的免疫反应，从而增强药物的影响。与竞争对手的治疗方案相比，该解决方案应该会大幅减少副作用。这种方法允许现成的分娩，使居住在偏远地区的患者能够获得最先进的治疗。在美国，每年花费在黑色素瘤治疗上的资金为57亿美元。针对III和IV期疾病的药物占15亿美元(26%)。这个小型企业技术转移(STTR)项目旨在证明超级携带者将治疗III期和IV期黑色素瘤的概念。该应用使用月桂酰单苯酮来产生选择性的抗黑色素瘤作用和有效的免疫激活，将药物包装在生物兼容的纳米脂质体颗粒中，用于选择性黑色素瘤的输送。该设计通过将活性成分直接输送到肿瘤来提高疗效，同时将副作用降至最低。由于肿瘤细胞而不是健康组织选择性地摄取纳米颗粒，而且只有当纳米颗粒进入溶酶体/黑素小体隔室时，超载体内容物才会释放，因此影响将主要(如果不是唯一的话)由肿瘤感受到。酪氨酸酶将前体药物转化为半抗黑素体酶(S)，以产生新的抗原，增加T细胞的可见度。由此产生的直接和间接的黑色素瘤细胞毒性是超级载体治疗成功的关键。毒性低，结合简单的现成交付，提高了患者的生活质量。由于增强的免疫活性不需要针对患者量身定做，因此该应用程序允许使用方便，并具有诱人的性价比。灵活、离家近的药物递送、几乎没有副作用、低成本和延长的预期寿命预计将建立药物的声誉，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智力优势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.