Li Chunying, Wan Yilin, Zhang Yifan, Fu Lian-Hua, Blum Nicholas Thomas, Cui Run, Wu Boda, Zheng Rui, Lin Jing, Li Zhiming, Huang Peng
Department of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060, China.
Adv Mater. 2022 Feb;34(5):e2103980. doi: 10.1002/adma.202103980. Epub 2021 Dec 12.
Complete resection of isocitrate dehydrogenase 1 (IDH1) (R132H) glioma is unfeasible and the classic post-surgical chemo/radiotherapy suffers from high recurrence and low survival rate. IDH1 (R132H) cells are sensitive to low concentrations of glucose and high concentrations of reactive oxygen species (ROS) due to inherent metabolism reprograming. Hence, a starvation/chemodynamic therapeutic gel is developed to combat residual IDH1 (R132H) tumor cells after surgery. Briefly, glucose oxidase (GOx) is mineralized with manganese-doped calcium phosphate to form GOx@MnCaP nanoparticles, which are encapsulated into the fibrin gel (GOx@MnCaP@fibrin). After spraying gel in the surgical cavity, GOx catalyzes the oxidation of glucose in residual IDH1 (R132H) cells and produces H O . The generated H O is further converted into highly lethal hydroxyl radicals (•OH) by a Mn -mediated Fenton-like reaction to further kill the residual IDH1 (R132H) cells. The as-prepared starvation/chemodynamic therapeutic gel shows much higher therapeutic efficacy toward IDH1 (R132H) cells than IDH1 (WT) cells, and achieves long-term survival.
完全切除异柠檬酸脱氢酶1（IDH1）（R132H）胶质瘤是不可行的，经典的术后化疗/放疗存在高复发率和低生存率的问题。由于内在的代谢重编程，IDH1（R132H）细胞对低浓度葡萄糖和高浓度活性氧（ROS）敏感。因此，开发了一种饥饿/化学动力治疗凝胶来对抗术后残留的IDH1（R132H）肿瘤细胞。简而言之，葡萄糖氧化酶（GOx）用锰掺杂的磷酸钙矿化形成GOx@MnCaP纳米颗粒，将其封装在纤维蛋白凝胶中（GOx@MnCaP@纤维蛋白）。在手术腔内喷洒凝胶后，GOx催化残留IDH1（R132H）细胞中的葡萄糖氧化并产生H₂O₂。通过锰介导的类芬顿反应，生成的H₂O₂进一步转化为高致死性的羟基自由基（•OH），以进一步杀死残留的IDH1（R132H）细胞。所制备的饥饿/化学动力治疗凝胶对IDH1（R132H）细胞的治疗效果比对IDH1（野生型）细胞高得多，并实现了长期存活。
