2. Academic Validation
  3. Manipulating Radiation-Sensitive Z-DNA Conformation for Enhanced Radiotherapy

Manipulating Radiation-Sensitive Z-DNA Conformation for Enhanced Radiotherapy

  • Adv Mater. 2024 Jul;36(29):e2313991. doi: 10.1002/adma.202313991.
Dongmei Wang 1 2,  You Liao 1 2,  Hao Zeng 1 2,  Chenglu Gu 1 2,  Xue Wang 1 2,  Shuang Zhu 1,  Xihong Guo 1,  Jie Zhang 3,  Ziye Zheng 3,  Junfang Yan 3,  Fuquan Zhang 3,  Lingmi Hou 4,  Zhanjun Gu 1 2,  Baoyun Sun 1 2
Affiliations

Affiliations

  • 1 CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.
  • 2 College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3 Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
  • 4 Academician (Expert) Workstation, Breast Cancer Biotarget Laboratory, Medical Imaging Key Laboratory of Sichuan Province, Department of Breast and Thyroid Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, China.
PMID: 38692575 DOI: 10.1002/adma.202313991
Abstract

DNA double-strand breaks (DSBs) yield highly determines radiotherapy efficacy. However, improving the inherent radiosensitivity of tumor DNA to promote radiation-induced DSBs remains a challenge. Using theoretical and experimental models, the underexplored impact of Z-DNA conformations on radiosensitivity, yielding higher DSBs than other DNA conformations, is discovered. Thereout, a radiosensitization strategy focused on inducing Z-DNA conformation, utilizing CBL@HfO2 nanocapsules loaded with a Z-DNA inducer CBL0137, is proposed. A hollow mesoporous HfO2 (HM-HfO2) acts as a delivery and an energy depositor to promote Z-DNA breakage. The nanocapsule permits the smart DSBs accelerator that triggers its radiosensitization with irradiation stimulation. Impressively, the CBL@HfO2 facilitates the B-Z DNA conformational transition, augmenting DSBs about threefold stronger than irradiation alone, generating significant tumor suppression with a 30% cure rate. The approach enables DSBs augmentation by improving the inherent radiosensitivity of DNA. As such, it opens up an era of Z-DNA conformation manipulation in radiotherapy.

Keywords

CBL0137; DNA double‐strand breaks; Z‐DNA conformation; radiosensitization; radiotherapy.

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