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Updated: Aug 2, 2026
Photodynamic Therapy with Blended Conducting Polymer/Fullerene Nanoparticle Photosensitizers
Published on: October 28, 2015
GSH-Responsive Nano-Photosensitizer for Potentiating Photodynamic Therapy Through Multi-Pronged Synergistic
Yunong Ma1, Kexin Xu1, Jing Feng1
1Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning 530004, China.
Abstract:
Impeded by the limited light penetration of photodynamic therapy (PDT) to tissues and the hypoxic environment of solid tumors, the clinical therapeutic efficacy and application are below expectations. In this study, a glutathione (GSH)-responsive nano-photosensitizer, based on the chlorquinaldol (CQD)-loaded iron-containing nanorod composed of meso-tetra (4-carboxyphenyl) porphyrin (TCPP), was prepared to serve as the laser-ignited ferroptosis sensitizer to improve the tumoricidal effect of PDT. In the tumor microenvironment (TME) with elevated GSH levels, therapeutic cargos and ferrous ions are released and are accompanied by the degradation of the nano-photosensitizer and GSH exhaustion. This not only increases liable iron pool (LIP) accumulation by the released ferrous ions but also decreases glutathione peroxidase 4 (GPX4) activity by GSH exhaustion. Simultaneously, GSH exhaustion disrupts intracellular redox homeostasis, heightening NIR light irradiation-triggered photosensitive oxidative stress. Moreover, the released CQD elevates the level of intracellular reactive oxygen species (ROS), enabling the nanorods to gain an oxygen radical generation ability and enhancing the photosensitive oxidative therapeutic efficacy. Strikingly, CQD exacerbates the downregulation of GPX4 expression to promote the accumulation of lipid peroxides. Therefore, we herald a new paradigm for synergistically potentiating PDT based on the "all-in-one" nano-photosensitizer through the multi-pronged upregulation of ferroptosis sensitivity.
Insights
This study developed a novel nano-photosensitizer that enhances photodynamic therapy (PDT) by triggering ferroptosis in tumors. The innovative material improves tumoricidal effects by targeting the tumor microenvironment and increasing oxidative stress.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Photodynamic therapy (PDT) efficacy is limited by poor light penetration and tumor hypoxia.
- Solid tumors present a challenging microenvironment for conventional cancer treatments.
Purpose of the Study:
- To develop a glutathione (GSH)-responsive nano-photosensitizer for enhanced PDT and ferroptosis induction.
- To overcome the limitations of PDT in solid tumors through a synergistic approach.
Main Methods:
- Preparation of chlorquinaldol (CQD)-loaded iron-containing nanorods based on meso-tetra (4-carboxyphenyl) porphyrin (TCPP).
- Utilizing the tumor microenvironment's elevated GSH levels for targeted drug/ion release and nanorod degradation.
- Investigating the combined effects of GSH exhaustion, iron accumulation, and NIR light irradiation on tumor cells.
Main Results:
- The nano-photosensitizer effectively releases therapeutic cargos and ferrous ions in the TME, increasing the labile iron pool (LIP).
- GSH exhaustion by the nanorods depletes glutathione peroxidase 4 (GPX4) activity, disrupting redox homeostasis.
- CQD release enhances reactive oxygen species (ROS) generation and exacerbates GPX4 downregulation, promoting lipid peroxide accumulation and ferroptosis.
Conclusions:
- A novel 'all-in-one' nano-photosensitizer synergistically potentiates PDT by upregulating ferroptosis sensitivity.
- This approach offers a promising strategy to improve tumoricidal effects against solid tumors.
- The developed nanorods demonstrate enhanced therapeutic efficacy through multi-pronged ferroptosis induction.
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