Hydrogel loading functionalized PAMAM/shRNA complex for postsurgical glioblastoma treatment

Glioblastoma, the most common malignant tumor of the central nervous system, readily relapses after surgery. Based on the CD47-SIRPα axis, we designed and implanted a thermo-sensitive hydrogel loaded with a gene complex into the postoperative cavity to inhibit the immune escape of residual tumor cells after surgery. A novel non-viral vector, G5-BGG, was synthesized and formed into a gene complex with shRNA plasmid. Our results showed that the G5-BGG/shRNA871 complex downregulated CD47 protein expression, leading to enhanced phagocytosis of U87MG cells by marrow-derived macrophages. G5-BGG/pDNA complex was loaded into a poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel. Studies confirmed that the G5-BGG/pDNA complex remained integrated in the hydrogel and was sustainably released for up to 7 days. In an in vivo orthotopic U87MG postoperative tumor model, G5-BGG/shRNA871-loaded hydrogel combined with temozolomide downregulated CD47 protein expression, increased macrophage infiltration into residual tumors, and significantly prolonged the survival time of mice, indicating potential applications for glioblastoma treatment.