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Engineering Magnesium Oxide as a Mitochondrial Electron Transport Chain Inhibitor for Enhanced Photodynamic Therapy
Liang Zhang1, Ting Wang1, Yunyi Shan1
1Department of Pharmaceutics, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 210009, China.
Molecular Pharmaceutics
|July 9, 2025
Summary
This study introduces MgO-ICG@S, a novel biocompatible agent that blocks mitochondrial respiration and delivers photosensitizers to triple-negative breast cancer (TNBC) cells, enhancing treatment efficacy.
Area of Science:
- Biochemistry
- Nanomedicine
- Oncology
Background:
- Triple-negative breast cancer (TNBC) is aggressive with few treatments.
- TNBC relies on oxidative phosphorylation (OXPHOS) for energy.
- Current mitochondrial electron transport chain (ETC) inhibitors have high toxicity.
Purpose of the Study:
- To develop a biocompatible agent for targeted TNBC therapy.
- To combine ETC inhibition with photodynamic therapy (PDT).
- To investigate a synergistic approach for enhanced antitumor effects.
Main Methods:
- Developed MgO-ICG suspension (MgO-ICG@S) using magnesium oxide (MgO) and indocyanine green (ICG).
- Utilized MgO for bidirectional ETC blockade and ICG as a mitochondria-targeted photosensitizer.
- Activated ICG with laser irradiation to generate reactive oxygen species (ROS).
Main Results:
- MgO-ICG@S effectively blocked ETC and disrupted mitochondrial function.
- Laser-activated ICG produced ROS, sensitizing TNBC cells to ETC inhibition.
- The combined ETC blockade and PDT demonstrated synergistic antitumor effects.
Conclusions:
- MgO-ICG@S offers a promising strategy for targeted TNBC treatment.
- This approach enhances therapeutic outcomes by combining ETC inhibition and PDT.
- Provides insights into developing biocompatible ETC-blocking agents for clinical use.
