Postoperative Injection of a Triptolide-Preloaded Hydrogel Prevents the Recurrence of Glioblastoma by Dual-Pathway Activation of Ferroptosis.

Autor: Wu H; Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, P. R. China.; Wuxi Key Laboratory of Biomaterials for Clinical Application, Key Laboratory for Multidisciplinary Intersection of Radiotherapy and Immunology for Gastrointestinal Tumor, Department of Central Laboratory, Jiangyin Clinical College of Xuzhou Medical University, Wuxi, Jiangsu, 214499, P. R. China., Cao P; Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, P. R. China., Wang H; Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, P. R. China.; Department of Digestive Endoscopy, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, P. R. China., Wang W; Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, P. R. China.; College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, P. R. China., Yu H; Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, P. R. China., You C; Jiangsu Key Lab for the Chemistry and Utilization of Agro-Forest Biomass, College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, P. R. China., Shen T; Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, P. R. China., Yang S; Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, P. R. China., Hu Z; Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, P. R. China., Zhou T; Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, P. R. China., Wang J; Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, P. R. China., Wang Q; Department of Bioinformatics, Nanjing Medical University, Nanjing, 211166, P. R. China.; Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, P. R. China., Qian X; Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, P. R. China.; Department of Nutrition and Food Hygiene, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, P. R. China., Zhang J; Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, P. R. China.; Department of Neurosurgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, P. R. China., Wang X; Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, P. R. China.; Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, P. R. China., Cao Y; Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, P. R. China.; Department of Radiation Oncology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, P. R. China., Ning L; Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, P. R. China., Lin F; Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, P. R. China.; Institute for Brain Tumors, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, P. R. China.; Department of Gastroenterology, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, 471023, P. R. China.
Jazyk: angličtina
Zdroj: Small (Weinheim an der Bergstrasse, Germany) [Small] 2024 Dec; Vol. 20 (50), pp. e2406036. Date of Electronic Publication: 2024 Oct 07.
DOI: 10.1002/smll.202406036
Abstrakt: Glioblastoma (GBM) recurrence leads to high mortality, which remains a major concern in clinical therapy. Herein, an injectable triptolide (TP)-preloaded hydrogel (TP@DNH) accompanied by a postoperative injection strategy is developed to prevent the recurrence of GBM. With a potential inhibitor of the NRF2/SLC7A11/GPX4 axis, it is demonstrated that TP can deactivate glutathione peroxidase 4 (GPX4) from the source of glutathione (GSH) biosynthesis, thereby activating ferroptosis in GBM cells by blocking the neutralization of intracellular lipid peroxide (LPO). Based on acid-sensitive Fe 3+ /tannic acid (TA) metal-phenolic networks (MPNs), the TP@DNH hydrogel can induce the effective generation of reactive oxygen species (ROS) through Fe 3+ /TA-mediated Fenton reaction and achieve controllable release of TP in resected GBM cavity. Due to ROS generation and GPX4 deactivation, postoperative injection of TP@DNH can achieve high-level ferroptosis through dual-pathway LPO accumulation, remarkably suppressing the growth of recurrent GBM and prolonging the overall survival in orthotopic GBM relapse mouse model. This work provides an alternative paradigm for regulating ferroptosis in the postoperative treatment of GBM.
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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