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A Novel Fluorescent Dye Invades Mitochondria to Selectively Kill Cancer Stem Cells via Increased ROS Production
Bei-Bei Zhang1, Jun-Gang Liu2, Xian-Yu Bai3
1Institute of Biomedical Research, Yunnan University, Kunming, China.
Abstract:
Development of multiple agents has a significant impact on the cancer diagnosis and therapy. Several fluorescent dyes including near-infrared (NIR) fluorescent agents have been already well studied in the field of photodynamic therapy (PDT). In the present study, we reported a novel fluorescent dye could obviously inhibit cancer cell proliferation with slight toxic effects on the biological organism. Furthermore, it displayed selective staining on cancer cells, particularly on cancer stem cells (CSCs), rather than normal cells. Mechanically, this dye preferred to invading mitochondria of cancer cells and inducing overwhelming reactive oxygen species (ROS) production. The in vivo experiments further demonstrated that this dye could image cancer cells and even CSCs in a short-time intratumor injection manner using a zebrafish model and subsequently inhibit cancer cell proliferation after a relatively long-time drug exposure. Taken together, the future development of this agent will promise to make an essential contribution to the cancer diagnosis and therapeutics.
Insights
A novel fluorescent dye selectively targets cancer stem cells (CSCs) and mitochondria, inhibiting cancer growth with minimal toxicity. This agent shows promise for advanced cancer diagnosis and photodynamic therapy (PDT).
Area of Science:
- Biomedical Engineering
- Cancer Research
- Photodynamic Therapy
Background:
- Fluorescent dyes, including near-infrared (NIR) agents, are crucial in cancer diagnosis and therapy.
- Photodynamic therapy (PDT) utilizes light-activated agents to treat cancer.
Purpose of the Study:
- To develop and evaluate a novel fluorescent dye for cancer diagnosis and therapy.
- To investigate the dye's selectivity for cancer cells, particularly cancer stem cells (CSCs).
- To elucidate the mechanism of action, including mitochondrial targeting and reactive oxygen species (ROS) generation.
Main Methods:
- Synthesis and characterization of a novel fluorescent dye.
- In vitro assessment of cancer cell proliferation inhibition and selectivity.
- Mitochondrial localization studies and ROS production analysis.
- In vivo imaging and therapeutic efficacy studies in a zebrafish model.
Main Results:
- The novel fluorescent dye demonstrated significant inhibition of cancer cell proliferation with low toxicity.
- Selective staining of cancer cells, especially CSCs, was observed.
- The dye preferentially localized to cancer cell mitochondria, inducing substantial ROS production.
- In vivo studies confirmed rapid cancer cell and CSC imaging and subsequent proliferation inhibition.
Conclusions:
- This novel fluorescent dye exhibits potential as a theranostic agent for cancer.
- Its ability to target CSCs and induce ROS offers a promising strategy for cancer treatment.
- Further development could lead to significant advancements in cancer diagnosis and PDT.
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