Hydrogel loading functionalized PAMAM/shRNA complex for postsurgical glioblastoma treatment
Hydrogel loading functionalized PAMAM/shRNA complex for postsurgical glioblastoma treatment
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DOI：
10.1016/j.jconrel.2021.08.052
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Min Liu
中科院分区：
文献类型：
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作者：
Song Jie;Han Zhang;Dongli Wang;Jing Wang;Jianfen Zhou;Zhiyi Zhang;Jun Wang;Yang Hu;Weixia Xu;Cao Xie;Weiyue Lu;Min Liu
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
