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Cancer-cell-specific Self-Reporting Photosensitizer for Precise Identification and Ablation of Cancer Cells
Ruoyao Zhang1, Chen Zhang1, Qing Lu2
1School of Medical Technology, Institute of Engineering Medicine, Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, Beijing Institute of Technology, Beijing 100081, China.
Abstract:
Cancer-cell-specific fluorescent photosensitizers (PSs) are highly desired molecular tools for cancer ablation with minimal damage to normal cells. However, such PSs that can achieve cancer specification and ablation and a self-reporting manner concurrently are rarely reported and still an extremely challenging task. Herein, we have proposed a feasible strategy and conceived a series of fluorescent PSs based on simple chemical structures for identifying and killing cancer cells as well as monitoring the photodynamic therapy (PDT) process by visualizing the change of subcellular localization. All of the constructed cationic molecules could stain mitochondria in cancer cells, identify cancer cells specifically, and monitor cancer cell viability. Among these, IVP-Br has the strongest ability to produce ROS, which serves as a potent PS for specific recognition and killing of cancer cells. IVP-Br could translocate from mitochondria to the nucleolus during PDT, self-reporting the entire therapeutic process. Mechanism study confirms that IVP-Br with light irradiation causes cancer cell ablation via inducing cell cycle arrest, cell apoptosis, and autophagy. The efficient ablation of tumor through PDT induced by IVP-Br has been confirmed in the 3D tumor spheroid chip. Particularly, IVP-Br could discriminate cancer cells from white blood cells (WBCs), exhibiting great potential to identify circulating tumor cells (CTCs).
Insights
Researchers developed novel fluorescent photosensitizers (PSs) for targeted cancer cell killing and therapy monitoring. One compound, IVP-Br, effectively eliminates cancer cells and distinguishes them from white blood cells.
Area of Science:
- Biomedical Engineering
- Photodynamic Therapy
- Molecular Imaging
Background:
- Developing cancer-specific photosensitizers (PSs) for effective ablation with minimal damage to healthy cells is crucial.
- Simultaneous cancer identification, ablation, and therapy monitoring via self-reporting PSs remain a significant challenge.
Purpose of the Study:
- To design and synthesize novel fluorescent PSs capable of specific cancer cell targeting, photodynamic ablation, and real-time therapy monitoring.
- To evaluate the efficacy of these PSs in vitro and in a 3D tumor spheroid model.
- To investigate the potential of these PSs in discriminating cancer cells from normal cells, including white blood cells.
Main Methods:
- Synthesis of a series of cationic fluorescent PSs.
- Evaluation of mitochondrial localization and cancer cell specificity.
- Assessment of reactive oxygen species (ROS) generation and photodynamic ablation efficacy.
- Monitoring of subcellular localization changes during photodynamic therapy (PDT).
- Mechanism studies involving cell cycle arrest, apoptosis, and autophagy induction.
- In vitro testing using 3D tumor spheroid chips and differentiation from white blood cells.
Main Results:
- All synthesized cationic molecules effectively stained mitochondria, specifically identified cancer cells, and monitored viability.
- IVP-Br demonstrated potent ROS generation and efficient cancer cell killing.
- IVP-Br exhibited a unique translocation from mitochondria to the nucleolus during PDT, enabling self-reporting of the therapeutic process.
- IVP-Br induced cancer cell ablation via cell cycle arrest, apoptosis, and autophagy.
- Successful tumor ablation was confirmed in 3D tumor spheroid models.
- IVP-Br effectively differentiated cancer cells from white blood cells, showing potential for circulating tumor cell detection.
Conclusions:
- A series of novel fluorescent PSs were developed for targeted cancer therapy and monitoring.
- IVP-Br is a promising photosensitizer for specific cancer cell recognition, photodynamic ablation, and real-time therapy visualization.
- IVP-Br's ability to discriminate cancer cells from WBCs highlights its potential for identifying circulating tumor cells.
