脑胶质瘤呈浸润性生长，手术不能完全切除肿瘤病灶，术后极易复发。我们前期工作证明：一种基于 “胍基-磷酸”分子识别的间苯双胍-PAMAM/pDNA水凝胶基因递释系统，瘤旁注射，瞬间胶凝，然后在15天内缓慢溶蚀释放基因，肿瘤组织可持续表达相关蛋白。本项目将进一步研究间苯双胍-PAMAM的胍基与DNA的磷酸的分子间距、热力学参数和分子识别作用机制，及其构建的水凝胶基因递释系统的流变学性能、溶蚀能力、DNA存在形式和DNA释放行为、细胞相容性和对肿瘤细胞上免疫检查点蛋白抑制作用，以及评价脑胶质瘤术后区域注射间苯双胍-PAMAM/pDNA水凝胶基因递释系统的动物模型中位生存期、脑肿瘤复发率、免疫检查点蛋白含量及其mRNA水平、抗肿瘤免疫机制和对正常脑组织的损伤。这些研究将对寻找一种有效降低脑肿瘤死亡率和复发率的治疗策略具有理论和实际意义

The glioma is difficult to resect completely due to the invasive growth in the brain, which results in relapse easily. In our previous studies, we have designed and prepared an isophthaloyl(oxy)bisguanidine-PAMAM hydrogel gene delivery system based on molecular recognition between guanidyl and phosphate. Once injected to the peritumoral site, the drug delivery system above could become gelation instantly then released the DNA slowly along with the gel degradation. Then the residual tumor could express associated proteins continuously after gene transfection..In this project, we plan to study further for the application of the hydrogel gene delivery system above from the following aspects. Firstly, the intermolecular distance, thermodynamic parameters and the mechanism of molecular recognition will be investigated. Then rheological properties, degradation rate of hydrogel, DNA existence form and DNA release behavior will be evaluated. Besides, the efficacy of gene silence in vitro, as well as the bio-compatibility will be also investigated. Finally, we will study the mechanism of the anti-tumor effect and the systematic safety using postoperative glioma animal models by analyzing the median survival time, the recurrence rate as well as the expression level of the immune checkpoint mRNA and protein. This study would contribute to developing a potential anti-glioma strategy in theory and practice, which could hopefully decrease the death and recurrence rates significantly.