Manipulating Radiation-Sensitive Z-DNA Conformation for Enhanced Radiotherapy.

Area of Science:

• Biophysics
• Radiotherapy
• Nanomedicine

Background:

• Radiotherapy efficacy is determined by DNA double-strand breaks (DSBs).
• Enhancing tumor radiosensitivity to increase DSBs remains a challenge.
• The role of Z-DNA conformations in radiosensitivity is underexplored.

Purpose of the Study:

• To investigate the impact of Z-DNA conformations on radiosensitivity.
• To develop a novel radiosensitization strategy using Z-DNA induction.
• To evaluate the efficacy of Z-DNA induction in combination with radiotherapy.

Main Methods:

• Theoretical and experimental modeling of DNA conformations.
• Development of CBL@HfO2 nanocapsules loaded with Z-DNA inducer CBL0137.
• Utilizing hollow mesoporous HfO2 (HM-HfO2) as a delivery and energy deposition agent.
• Assessing the B-Z DNA conformational transition and its effect on DSBs.

Main Results:

• Z-DNA conformations yield higher DSBs compared to other DNA forms.
• CBL@HfO2 nanocapsules facilitate B-Z DNA transition, augmenting DSBs threefold.
• The strategy significantly enhances tumor suppression, achieving a 30% cure rate.
• The approach improves inherent DNA radiosensitivity, leading to augmented DSBs.

Conclusions:

• Inducing Z-DNA conformation is a viable radiosensitization strategy.
• CBL@HfO2 nanocapsules effectively promote Z-DNA formation and enhance radiotherapy.
• This work opens new avenues for Z-DNA conformation manipulation in cancer treatment.