Injectable oxidized high-amylose starch hydrogel scaffold for macrophage-mediated glioblastoma therapy

Glioblastoma, characterized by rapid proliferation and invasiveness, is largely resistant to current treatment modalities. A major obstacle is the blood-brain barrier (BBB), which restricts the delivery of therapeutic agents as well as the infiltration of effective immune cells into glioblastoma. In this study, we developed an injectable oxidized high-amylose starch hydrogel (OHASM) to serve as a biomaterial scaffold for the delivery of macrophages and macrophage-polarizing drugs, aiming to bypass the BBB and enhance glioblastoma treatment. The in vitro and in vivo experiments confirmed the efficacy of the hydrogel in loading and delivering macrophages and polarizing drugs against glioblastoma. Additionally, the hydrogel's interconnected porous structure was conducive to cellular growth and activity, and its slow release of therapeutics contributed to the extended survival of treated mice in a mouse GL261 glioblastoma tumor model. The immunological mechanisms underlying the therapeutic efficacy were further elucidated, revealing the potential of the hydrogel system to modulate macrophage polarization and induce apoptosis in tumor cells via the poly ADP-ribose polymerase (PARP) pathway. The study underscores the potential of the hydrogel-based macrophage delivery strategy as an effective and safe treatment for glioblastoma, offering a promising avenue for clinical management of this aggressive brain cancer.