Methioninase Loaded Nanoshells for Systemic Methionine Depletion Therapy

DESCRIPTION (provided by applicant): Systemic depletion of the essential amino acid methionine has been shown to be a potentially powerful therapeutic approach to many cancer types. A critical gene in the methionine salvage pathway, MTAP, is co- deleted along with the chromosomally co-located CDKN2A gene in a large number of solid tumors. However, attempts to use methioninase as a therapy failed because of rapid in vivo co-factor loss. Methioninase requires pyridoxal phosphate (PLP), the activated form of vitamin B6, but PLP is rapidly sequestered by albumin in blood. The goal of this proposal is to enable methioninase therapy by encapsulating it in a novel nanoparticle termed synthetic hollow enzyme loaded sphere (SHELS). SHELS are made of a thin layer of silica templated on polystyrene spheres with smaller spheres bound to the surface as masks. Once silica is grown and the templates and masks burned away, silica shells with large pores our formed. The methioninase is loaded through these pores and enca