Proteinated Subnano Particles of Elemental Selenium for the Treatment of Breast Cancer

摘要

The purpose of this award is to test in preclinical models the hypothesis that cytotoxic conjugates of elemental selenium and proteins are safe and effective for the systemic therapy of invasive breast cancer. The grant has three specific aims, (1) to evaluate the safety and efficacy of systemically administered Se(0)-protein conjugates in athymic nude mice bearing xenografts of human breast cancer cells, (2) to assess the functional integrity of conjugate-treated normal human hematopoietic stem cells, and (3) to determine by use of the combination index method how Se(0)-protein conjugates interact with standard chemotherapeutic agents that are commonly used in the treatment of breast cancer. We report here on the development and evaluation of improved methods for the generation of high-potency cytotoxic Se(0)-protein conjugates, the interactions of Se(0)-protein conjugates with standard chemotherapeutic agents, and the interference of certain antibiotics with the photochemical generation of Se(0)-protein conjugates.