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A Salidroside-Based Radiosensitizer Regulates the Nrf2/ROS Pathway for X-Ray Activated Synergistic Cancer Precise
Qingqing Li1, Qing Chen2, Shenggan Xiao1
1Fujian Science & Technology Innovation Laboratory for Optoelectronic Information of China, College of Chemistry, Fuzhou University, Fuzhou, 350108, China.
Abstract:
The hypoxic microenvironment and radioresistance of tumor cells, as well as the delay in efficacy evaluation, significantly limit the effect of clinical radiotherapy. Therefore, developing effective radiosensitizers with monitoring of tumor response is of great significance for precise radiotherapy. Herein, a novel radiosensitizer (term as: SCuFs) is developed, consisting of traditional Chinese medicine (TCM) compounds salidroside, Cu2+, and hydroxyl radical (•OH) activated second near-infrared window fluorescence (NIR-II FL) molecules, which make the radiosensitization effect and boosted chemodynamic therapy (CDT) efficacy. The overexpressed glutathione in the tumor induces the SCuFs dissociation, allowing deep penetration of the drug to the whole tumor region. After X-ray irradiation, salidroside inhibits the Nuclear factor erythroid 2-like 2 (Nrf2)protein expression and blocks cells in the G2/M phase with the highest radiosensitivity, which amplifies the reactive oxygen species (ROS) generation to exacerbate DNA damage, thus achieving radiosensitization. Meanwhile, the upregulated ROS provides sufficient chemical fuel for Cu+-mediated CDT to produce more •OH. NIR-II FL imaging can monitor the •OH changes during the therapy process, confirming the radiosensitization effect and CDT process related to •OH. This study not only achieves effective radiosensitization and cascaded ROS-mediated CDT efficacy, but also provides a useful tool for monitoring therapeutic efficacy, showing great prospects for clinical application.
Insights
A novel radiosensitizer, SCuFs, enhances radiotherapy by boosting chemodynamic therapy and enabling real-time monitoring. This approach overcomes tumor hypoxia and radioresistance for more effective cancer treatment.
Area of Science:
- Biomedical Engineering
- Radiotherapy
- Nanomedicine
Background:
- Tumor hypoxia and radioresistance limit radiotherapy efficacy.
- Delayed efficacy evaluation hinders precise radiotherapy.
- Developing effective radiosensitizers with response monitoring is crucial.
Purpose of the Study:
- To develop a novel radiosensitizer (SCuFs) for enhanced radiotherapy and chemodynamic therapy (CDT).
- To enable real-time monitoring of therapeutic efficacy using NIR-II fluorescence imaging.
- To overcome tumor hypoxia and radioresistance for improved clinical outcomes.
Main Methods:
- SCuFs synthesized from salidroside, Cu2+, and NIR-II FL molecules.
- Glutathione-induced SCuFs dissociation for deep tumor penetration.
- X-ray irradiation triggers salidroside to inhibit Nrf2 and amplify ROS generation.
- Cu+-mediated CDT utilizes ROS to produce hydroxyl radicals (•OH).
- NIR-II FL imaging monitors •OH changes for therapy assessment.
Main Results:
- SCuFs achieved significant radiosensitization by blocking cells in the G2/M phase.
- Enhanced ROS generation amplified DNA damage and boosted CDT efficacy.
- NIR-II FL imaging successfully monitored •OH production, confirming therapeutic processes.
- The combined therapy demonstrated effective radiosensitization and cascaded ROS-mediated CDT.
Conclusions:
- SCuFs effectively enhance radiotherapy and CDT, overcoming tumor hypoxia and radioresistance.
- The developed system provides real-time monitoring of therapeutic response.
- This approach shows significant promise for precise radiotherapy applications.
