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A Salidroside-Based Radiosensitizer Regulates the Nrf2/ROS Pathway for X-Ray Activated Synergistic Cancer Precise

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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.

Keywords:
NIR‐II fluorescenceactivatable probein vivo bioimagingradiotherapyself‐assembly

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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.