Pickering emulsion templated proteinaceous microparticles as glutathione-responsive carriers for endocytosis in tumor cells

Abstract

The use of glucose oxidase (GOx) to disrupt glucose supply has been identified as a promising strategy in cancer starvation therapy. However, independent delivery of GOx is prone to degradation upon exposure to biological conditions and may cause damage to blood vessels and normal organs during transportation. Although some carriers can protect GOx from the surrounding environment, the harsh preparation conditions may compromise its activity. Moreover, the commonly used materials often exhibit poor biocompatibility and possess certain cytotoxicity. To address this issue, we developed a gentle and efficient method based on Pickering emulsion templates to synthesize protein-based microparticles using zein as the matrix material. These microparticles have high stability and can be tailored to efficiently encapsulate biomolecules while preserving their activity. Moreover, the zein-based microparticles can be triggered to release biomolecules in tumor cells under high glutathione levels, demonstrating excellent responsiveness, biocompatibility, and low cytotoxicity. Additionally, when loaded with GOx, these protein-based microparticles effectively deprive tumor cells of nutrients and induce apoptosis by generating high levels of H₂O₂, thereby exhibiting enhanced anticancer properties.