Related Experiment Video
Updated: Oct 14, 2025
Magnetic-, Acoustic-, and Optical-Triple-Responsive Microbubbles for Magnetic Hyperthermia and Pothotothermal Combination Cancer Therapy
Published on: May 22, 2020
Tumor microenvironments self-activated nanoscale metal-organic frameworks for ferroptosis based cancer
Yu Liang1,2, Li Zhang1, Chao Peng1,2,3
1Department of Medicine Ultrasonics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Abstract:
Ferroptosis, as a newly discovered cell death form, has become an attractive target for precision cancer therapy. Several ferroptosis therapy strategies based on nanotechnology have been reported by either increasing intracellular iron levels or by inhibition of glutathione (GSH)-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4). However, the strategy by simultaneous iron delivery and GPX4 inhibition has rarely been reported. Herein, novel tumor microenvironments (TME)-activated metal-organic frameworks involving Fe & Cu ions bridged by disulfide bonds with PEGylation (FCSP MOFs) were developed, which would be degraded specifically under the redox TME, simultaneously achieving GSH-depletion induced GPX4 inactivation and releasing Fe ions to produce ROS via Fenton reaction, therefore causing ferroptosis. More ROS could be generated by the acceleration of Fenton reaction due to the released Cu ions and the intrinsic photothermal capability of FCSP MOFs. The overexpressed GSH and H2O2 in TME could ensure the specific TME self-activated therapy. Better tumor therapeutic efficiency could be achieved by doxorubicin (DOX) loading since it can not only cause apoptosis, but also indirectly produce H2O2 to amplify Fenton reaction. Remarkable anti-tumor effect of obtained FCSP@DOX MOFs was verified via both in vitro and in vivo assays.
Insights
This study introduces novel metal-organic frameworks that simultaneously deliver iron and inhibit GPX4 to induce ferroptosis, offering a new precision cancer therapy strategy. These frameworks are activated by the tumor microenvironment for targeted cancer cell death.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Ferroptosis, a distinct form of cell death, is a promising target for precision cancer therapy.
- Current nanotech strategies focus on iron delivery or GPX4 inhibition, but simultaneous approaches are underexplored.
Purpose of the Study:
- To develop novel tumor microenvironment (TME)-activated metal-organic frameworks (MOFs) for simultaneous iron delivery and GPX4 inhibition.
- To induce ferroptosis specifically within the TME for enhanced cancer treatment.
Main Methods:
- Designed PEGylated Fe & Cu ion-bridged disulfide-bonded MOFs (FCSP MOFs) activated by TME redox conditions.
- Investigated TME-triggered degradation, GSH depletion, GPX4 inactivation, iron release, and ROS generation via Fenton reaction.
- Incorporated doxorubicin (DOX) to enhance ROS production and apoptosis.
Main Results:
- FCSP MOFs demonstrated TME-specific activation, leading to GSH depletion and GPX4 inactivation.
- Simultaneous iron release and Fenton reaction, accelerated by Cu ions and photothermal effects, generated significant ROS.
- FCSP@DOX MOFs exhibited remarkable in vitro and in vivo anti-tumor efficacy, amplified by DOX-induced H2O2 production.
Conclusions:
- Novel TME-activated FCSP MOFs effectively induce ferroptosis through simultaneous iron delivery and GPX4 inhibition.
- The combination therapy approach, enhanced with DOX, shows significant potential for precision cancer treatment.
- This strategy offers a new avenue for developing targeted nanomedicines against cancer.
More Related Videos
09:23Inducing Targeted Mild Hyperthermia in Murine Tumor Models through Photothermal Conversion of Near-infrared Light by Intratumoral Gold Nanorods
Published on: October 10, 2025
04:53Author Spotlight: Advances in Evaluating Human Lung Epithelial Cells' Response to Metal-Organic Frameworks
Published on: May 26, 2023