Related Experiment Video
Updated: Jun 4, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Self-augmented catabolism mediated by Se/Fe co-doped bioceramics boosts ROS storm for highly efficient antitumor
Wenjing Yang1, Chenhang Ding1, Yibing Ji1
1Jiangxi Province Key Laboratory of Additive Manufacturing of Implantable Medical Device, Jiangxi University of Science and Technology, Nanchang 330013, China.
Abstract:
The overexpression of glutathione (GSH) within the tumor microenvironment has long been considered as the major obstacle for reactive oxygen species (ROS)-based antitumor therapies. To address this challenge, a selenite (SeO32 -) and ferric ion co-doped hydroxyapatite (SF-HAP) nanohybrid was synthesized, which is then introduced into poly-L-lactic acid (PLLA) to prepare porous scaffold by selective laser sintering to continuously release Fe3+ and SeO32- ions. Of great significance is the released SeO32- catabolize GSH to generate superoxide anion (O2•-) rather than directly eliminating GSH, thereby reversing the obstacle posed by its overexpression and achieving a "waste-to-treasure" transformation. The newly generated O2•- synergizes with the hydroxyl radicals (•OH) produced by the Fenton reaction between Fe3+/2+ and hydrogen peroxide, triggering high concentration ROS storms. Collectively, the PLLA/SF-HAP scaffold mediated self-augmented catabolism dynamic progress significantly raised intracellular ROS levels, almost twice as much as PLLA/Fe-HAP scaffold, thereby effectively inducing tumor cell apoptosis. The study provides an innovative inspiration for ROS-based antitumor therapies.
Insights
This study developed a novel nanohybrid scaffold that converts tumor glutathione into beneficial superoxide anions. This approach enhances reactive oxygen species (ROS) levels, overcoming a major obstacle in ROS-based cancer therapies.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapy
Background:
- Glutathione (GSH) overexpression in tumors hinders reactive oxygen species (ROS)-based therapies.
- Developing strategies to overcome GSH-induced resistance is crucial for effective cancer treatment.
Purpose of the Study:
- To synthesize a novel nanohybrid scaffold for overcoming GSH-mediated resistance in ROS-based cancer therapy.
- To investigate the synergistic effect of selenite and ferric ions in generating ROS and inducing tumor cell apoptosis.
Main Methods:
- Synthesis of selenite and ferric ion co-doped hydroxyapatite (SF-HAP) nanohybrid.
- Fabrication of porous poly-L-lactic acid (PLLA)/SF-HAP scaffolds using selective laser sintering.
- In vitro evaluation of ROS generation and tumor cell apoptosis induction.
Main Results:
- The PLLA/SF-HAP scaffold continuously released Fe3+ and SeO32- ions.
- Released selenite ions converted GSH into superoxide anions, enhancing ROS levels.
- The scaffold significantly increased intracellular ROS, leading to effective tumor cell apoptosis.
Conclusions:
- The developed PLLA/SF-HAP scaffold offers a promising strategy to reverse GSH-mediated resistance in ROS-based antitumor therapies.
- This approach represents an innovative advancement in designing effective cancer treatment modalities.
