SBIR Phase I: Targeted Small Molecular Taxane Delivery for Triple Negative Breast Cancer Treatment

Iria Pharma, Llc, Champaign IL

Investigators

Abstract

This SBIR Phase I project proposes to develop a novel cancer targeting technology, Active Tissue Targeting via Anchored ClicK Chemistry (ATTACK), for targeted treatment of triple negative breast cancer (TNBC). TNBC is a subtype of breast cancer that occurs in 10-20% of diagnosed breast cancers and is more likely to affect younger people, African Americans, Hispanics, and those with BRCA1 gene mutation. Currently, TNBC patients are mainly treated with chemotherapeutics and cannot benefit from existing targeting therapeutics due to the lack of Estrogen receptor (ER), progesterone receptor (PR) or hormone epidermal growth factor receptor 2 (Her2/neu). This project will develop the first cell labeling based targeting technology (ATTACK) for TNBC treatment. A novel unnatural sugar will be developed for cancer-specific labeling of TNBC through metabolization to insert an artificial receptor onto TNBC and then target the artificial receptor to deliver therapeutic taxanes through a specific reaction between the receptor and the taxanes-drugs. The project involves interdisciplinary combination of knowledge from chemistry, biology, materials engineering, and pharmaceutical science. The successful development of the project will afford an effective targeted therapeutic drug for TNBC patients with improved quality of life in the future. This SBIR Phase I project proposes to develop a novel cancer targeting technology, Active Tissue Targeting via Anchored ClicK Chemistry (ATTACK), for targeted treatment of triple negative breast cancer (TNBC). ATTACK can treat untargetable cancers that do not have established cell surface receptors through cancer-specific artificial receptor insertion of de novo designed unnatural sugars and subsequent azide-Click reaction mediated targeted delivery of therapeutic drugs. Currently, TNBC patients are mainly treated with chemotherapeutics and cannot benefit from existing targeting therapeutics due to the lack of Estrogen receptor (ER), progesterone receptor (PR) or hormone epidermal growth factor receptor 2 (Her2/neu). This project will develop the first cell labeling based targeting technology (ATTACK) for TNBC treatment. Unnatural sialic acid (a type of sugar) precursors with azide will be first used for tumor-specific labeling on cell surface and subsequent targeting. Multiple taxane candidates will be synthesized and preliminary in vitro DMPK properties of the conjugates will be studied including solubility, plasma stability, liver microsome metabolization, and cytotoxic MTT assay. In vivo biodistribution and efficacy of the taxane candidates in combination with unnatural sugar labeling will also be studied in mice tumor models to validate the anti-TNBC efficacy of the drug candidates. The accomplishment of the Phase I research will enable further translational development of the novel cancer-targeting therapeutics into clinical applications. 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.