Related Experiment Video
Updated: Jul 8, 2025
Magnetic-, Acoustic-, and Optical-Triple-Responsive Microbubbles for Magnetic Hyperthermia and Pothotothermal Combination Cancer Therapy
Published on: May 22, 2020
pH-Responsive Sorafenib/Iron-Co-Loaded Mesoporous Polydopamine Nanoparticles for Synergistic Ferroptosis and
Shang Liu1, Ying Liu2, Qing Chang1
1Institute of Nanochemistry and Nanobiology, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.
Abstract:
Ferroptosis has attracted significant attention as a new mechanism of cell death. Sorafenib (SRF) is widely considered a prototypical ferroptosis-inducing drug, particularly for liver cancer treatment. However, the low solubility and hydrophobic nature of SRF, along with the absence of synergistic therapeutic strategies, still limit its application in cancer treatment. Herein, we report a dual therapeutic method incorporating photothermal therapy and ferroptosis by using Fe-doped mesoporous polydopamine nanoparticles (Fe-mPDA@SRF-TPP) as a carrier for loading SRF and targeting triphenylphosphine (TPP). SRF molecules are efficiently encapsulated within the polydopamine nanospheres with a high loading ratio (80%) attributed to the porosity of Fe-mPDA, and the inherent biocompatibility and hydrophilicity of Fe-mPDA@SRF-TPP facilitate the transport of SRF to the target cancer cells. Under the external stimuli of acidic environment (pH 5.0), glutathione (GSH), and laser irradiation, Fe-mPDA@SRF-TPP shows sustained release of SRF and Fe ions with the ratio of 72 and 50% within 48 h. Fe-mPDA@SRF-TPP nanoparticles induce intracellular GSH depletion, inhibit glutathione peroxidase 4 (GPX4) activity, and generate hydroxyl radicals, all of which are essential components of the therapeutic ferroptosis process for killing MDA-MB-231 cancer cells. Additionally, the excellent near-infrared (NIR) light absorption of Fe-mPDA@SRF-TPP nanoparticles demonstrates their capability for photothermal therapy and further enhances the therapeutic efficiency. Therefore, this nanosystem provides a multifunctional therapeutic platform that overcomes the therapeutic limitations associated with standalone ferroptosis and enhances the therapeutic efficacy of SRF for breast cancer.
Insights
This study introduces a dual therapy using iron-doped nanoparticles to deliver sorafenib (SRF) for enhanced ferroptosis and photothermal cancer treatment, improving SRF
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Ferroptosis is a significant cell death mechanism with therapeutic potential, particularly in liver cancer.
- Sorafenib (SRF) is a ferroptosis inducer but faces limitations due to poor solubility and lack of synergistic strategies.
- Existing treatments require novel approaches to overcome drug limitations and enhance efficacy.
Purpose of the Study:
- To develop a dual therapeutic strategy combining photothermal therapy and ferroptosis for cancer treatment.
- To create a nanoparticle carrier (Fe-mPDA@SRF-TPP) for efficient SRF delivery and targeting.
- To evaluate the efficacy of the developed nanosystem in inducing ferroptosis and photothermal effects in cancer cells.
Main Methods:
- Synthesis of Fe-doped mesoporous polydopamine nanoparticles (Fe-mPDA) loaded with Sorafenib (SRF) and targeted with triphenylphosphine (TPP).
- Characterization of nanoparticle properties, including SRF loading efficiency and release kinetics under specific stimuli (acidic pH, GSH, laser).
- In vitro evaluation of nanoparticle-induced ferroptosis (GSH depletion, GPX4 inhibition, hydroxyl radical generation) and photothermal therapy efficacy in MDA-MB-231 cancer cells.
Main Results:
- Fe-mPDA@SRF-TPP nanoparticles achieved a high SRF loading ratio (80%) and exhibited sustained release of SRF and Fe ions.
- The nanoparticles effectively induced ferroptosis by depleting intracellular GSH, inhibiting GPX4 activity, and generating hydroxyl radicals.
- The Fe-mPDA@SRF-TPP nanoparticles demonstrated excellent near-infrared (NIR) light absorption, enabling effective photothermal therapy and enhancing overall therapeutic efficiency against breast cancer cells.
Conclusions:
- The developed Fe-mPDA@SRF-TPP nanosystem offers a multifunctional platform for combined ferroptosis and photothermal therapy.
- This approach overcomes the limitations of standalone ferroptosis and enhances the therapeutic efficacy of Sorafenib for breast cancer treatment.
- The synergistic therapeutic strategy holds promise for improving cancer treatment outcomes.
