Manipulating Radiation-Sensitive Z-DNA Conformation for Enhanced Radiotherapy.
Adv Mater
; 36(29): e2313991, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38692575
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA, Z-Form
/
DNA Breaks, Double-Stranded
/
Nucleic Acid Conformation
Limits:
Animals
/
Humans
Language:
En
Journal:
Adv Mater
Journal subject:
BIOFISICA
/
QUIMICA
Year:
2024
Document type:
Article
Affiliation country:
China