Project summary The goal of this proposal is to increase our understanding of the therapeutic benefits of using platelets for preventing the spread of cancer, or metastasis. Metastasis is the main cause of cancer-associated mortality that occurs when some cancer cells, also called circulating tumor cells (CTCs), detach from primary tumor sites and enter the bloodstream to invade other tissues and organs at different locations. The presence of CTCs in patients is associated with a poor prognosis because once CTCs enter the bloodstream it is difficult to prevent them from reaching secondary organs and spreading cancer. Therefore, targeting CTCs may represent a promising target for anticancer therapies. Once CTCs enter into the bloodstream, they face many survival challenges including immunological attack, shear forces, and apoptosis. To enhance their survival rate, CTCs strongly attract platelets to form a protective cloak that helps the cancer cells survive the forces in the bloodstream and to escape immune surveillance. Although the mechanisms by which platelets interact with circulating tumor cells are poorly understood, studies have shown that they are involved in cancer progress, especially during metastasis where platelets help to degrade extracellular matrix (ECM) to support the colonization of cancer cells in distant locations from the original tumor formation site. We propose to take advantage of platelets' innate association with circulating tumor cells and their storage, trafficking, and release capacities of small molecules, to engineer them as delivery vehicles for the development of next generation delivery methods for targeting and destroying CTCs to prevent or minimize metastasis.