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

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.