Related Experiment Video
Updated: Aug 12, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Fluorescence Imaging-Incorporated Transcriptome Study of Glutathione Depletion-Enhanced Ferroptosis Therapy via
Dan Zhao1, Xiaoyu Huang2, Yanan Tian2
1School of Environmental Science and Engineering, State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
Abstract:
Ferroptosis plays an important role in tumor inhibition and is a new type of programmed cell death. Recent studies have shown that glutathione (GSH) depletion is an effective method to enhance the therapeutic efficacy of ferroptosis; however, a systematic investigation of the phenomenon is limited. Herein, we provide a facile fluorescence imaging-incorporated transcriptome strategy to visualize the process and explore the mechanism of GSH depletion-enhanced ferroptosis. The proposed multifunctional nanoplatform is achieved using simple transferrin receptor aptamer-functionalized fluorescent gold nanoclusters (termed TfRA-AuNCs), which exhibit efficient hydroxyl radical generation and GSH-depleting capabilities. Live cell fluorescence imaging results revealed that TfRA-AuNCs were endocytosed into 4T1 cells and were mostly distributed in lysosomes. In vitro results indicated that TfRA-AuNCs enhanced the ferroptosis effect in 4T1 cells. Importantly, transcriptome analysis indicated that 4T1 cells treated with TfRA-AuNCs regulated the expression change of ferroptosis-related genes, and the Kyoto Encyclopedia of Genes and Genomes pathway identified the GSH metabolism pathway involved in ferroptosis, thus revealing the exact molecular mechanism of ferroptosis induced by TfRA-AuNCs at the RNA level. Furthermore, in vivo results confirmed the tumor inhibition effect, tumor-targeted fluorescence imaging, and long-term biocompatibility after TfRA-AuNC treatment. This study introduces a new possibility for the mechanistic study of nanoagent-induced ferroptosis in tumor treatment.
Insights
This study developed a novel nanoplatform to visualize and explore glutathione depletion-enhanced ferroptosis for tumor inhibition. The findings reveal molecular mechanisms and demonstrate therapeutic potential in vivo.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Ferroptosis, a type of programmed cell death, is crucial for tumor inhibition.
- Glutathione (GSH) depletion enhances ferroptosis efficacy, but its mechanisms require further investigation.
- Developing effective strategies for studying nanoagent-induced ferroptosis is essential for cancer therapy.
Purpose of the Study:
- To develop a fluorescence imaging-incorporated transcriptome strategy to visualize and explore GSH depletion-enhanced ferroptosis.
- To investigate the mechanism of action of transferrin receptor aptamer-functionalized fluorescent gold nanoclusters (TfRA-AuNCs) in ferroptosis.
- To evaluate the therapeutic efficacy and biocompatibility of TfRA-AuNCs in vitro and in vivo.
Main Methods:
- Fabrication of multifunctional TfRA-AuNCs with GSH-depleting and fluorescence imaging capabilities.
- Live cell fluorescence imaging to track TfRA-AuNCs uptake and distribution in 4T1 cells.
- Transcriptome analysis (RNA sequencing) to identify gene expression changes and pathways involved in ferroptosis.
- In vitro and in vivo experiments to assess ferroptosis enhancement, tumor inhibition, and biocompatibility.
Main Results:
- TfRA-AuNCs were efficiently internalized by 4T1 cells and localized in lysosomes.
- TfRA-AuNCs significantly enhanced ferroptosis in 4T1 cancer cells.
- Transcriptome analysis revealed that TfRA-AuNCs modulated ferroptosis-related gene expression, implicating the GSH metabolism pathway.
- In vivo studies confirmed tumor inhibition, targeted fluorescence imaging, and good biocompatibility of TfRA-AuNCs.
Conclusions:
- The developed TfRA-AuNCs provide a powerful tool for mechanistic studies of nanoagent-induced ferroptosis.
- This strategy offers a new approach for understanding and enhancing ferroptosis-based cancer therapy.
- The findings highlight the potential of TfRA-AuNCs for targeted tumor inhibition and imaging.
More Related Videos
09:11Synthesis of Near-Infrared Emitting Gold Nanoclusters for Biological Applications
Published on: March 22, 2020
09:22Author Spotlight: Direct Synthesis of EM-Visible Gold Nanoparticles in Cells for Protein Localization Analysis with Well-Preserved Ultrastructure
Published on: April 28, 2023