Cancer Cell-Sticky Hydrogels to Target the Cell Membrane of Invading Glioblastomas

Abstract

Owing to their remarkable infiltrative traits, glioblastomas develop unclear tumor margins toward the brain, hampering the complete resection. Since the remaining invasive cells tend to have resistance to therapeutics and cause recurrence around the surgical voids, this has been a major challenge for glioblastoma treatment. Thus, we design a cancer cell-sticky hydrogel (CSH) that interacts with the glioblastoma cells to impede their invasive motility by modifying the cell membrane with active thiol-enriched interfaces. Highly reactive thiols at the cell surface can make the infiltrated cancer cells adhere to the hydrogel, resulting in increased cell adhesion and decreased motility. Cotreatment with the CSH and chemical inhibitors of the major proinvasive molecules, focal adhesion kinase and hyaluronic acid synthase, maximized the invasion-inhibitory effect. In addition, a significant decrease in tumor mass was achieved via CSH implantation in mouse models. Overall, our results highlight the use of the CSH to inhibit the aggressive invasion as a novel therapeutic strategy against glioblastoma.