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

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<sup>3+</sup>/tannic acid (TA) metal-phenolic networks (MPNs), the TP@DNH hydrogel can induce the effective generation of reactive oxygen species (ROS) through Fe<sup>3+</sup>/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.

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Journal
Small
Published
2024-10-07
DOI
https://doi.org/10.1002/smll.202406036
Citations
12
Primary Topic
Ferroptosis and cancer prognosis
Type
article
Field-Weighted Citation Impact
5.03

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article

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

Chaoqun You, Qianghu Wang, Junxia Zhang, Xiuxing Wang et al.
12 citations
Small
Ferroptosis and cancer prognosis
5.03
article

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

Chaoqun You, Qianghu Wang, Junxia Zhang, Xiuxing Wang, Like Ning, Suisui Yang, Fan Lin, Yuandong Cao, Wenhong Wang, Hongshuai Wu, Tianqi Shen, Pingping Cao, Hanyang Yu, Haiyang Wang, Ziyi Hu, Qian Xu, Tingting Zhou, Jing Wang
article en
12 citations

Abstract

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<sup>3+</sup>/tannic acid (TA) metal-phenolic networks (MPNs), the TP@DNH hydrogel can induce the effective generation of reactive oxygen species (ROS) through Fe<sup>3+</sup>/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.

SmallVol. 20(50)
Nanjing Forestry University (CN), Xuzhou Medical College (CN), Jiangsu Cancer Hospital (CN), First Affiliated Hospital of Henan University of Science and Technology (CN), Zhejiang University of Technology (CN), Nanjing Medical University (CN)
National Natural Science Foundation of China
Good health and well-being
Openalex Percentile: Top 4%
Ferroptosis and cancer prognosis
5.03
DOIOpen Access PDFOpenAlex
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