Nitric Oxide‐Releasing Nanoscale Metal‐Organic Layer Overcomes Hypoxia and Reactive Oxygen Species Diffusion Barriers to Enhance Cancer Radiotherapy

Nitric Oxide‐Releasing Nanoscale Metal‐Organic Layer Overcomes Hypoxia and Reactive Oxygen Species Diffusion Barriers to Enhance Cancer Radiotherapy

Abstract Hafnium (Hf)‐based nanoscale metal‐organic layers (MOLs) enhance radiotherapeutic effects of tissue‐penetrating X‐rays via a unique radiotherapy‐radiodynamic therapy (RT‐RDT) process through efficient generation of hydroxy radical (RT) and singlet oxygen (RDT). However, their radiotherapeut...

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Bibliographic Details
Main Authors: Yuxuan Xiong, Jinhong Li, Xiaomin Jiang, Wenyao Zhen, Xin Ma, Wenbin Lin
Format: Article
Language:English
Published: Wiley 2025-02-01
Series:Advanced Science
Subjects:
hypoxia
metal‐organic layers
nitric oxide
radiotherapy
reactive oxygen species
Online Access:https://doi.org/10.1002/advs.202413518
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Summary:Abstract Hafnium (Hf)‐based nanoscale metal‐organic layers (MOLs) enhance radiotherapeutic effects of tissue‐penetrating X‐rays via a unique radiotherapy‐radiodynamic therapy (RT‐RDT) process through efficient generation of hydroxy radical (RT) and singlet oxygen (RDT). However, their radiotherapeutic efficacy is limited by hypoxia in deep‐seated tumors and short half‐lives of reactive oxygen species (ROS). Herein the conjugation of a nitric oxide (NO) donor, S‐nitroso‐N‐acetyl‐DL‐penicillamine (SNAP), to the Hf12 secondary building units (SBUs) of Hf‐5,5′‐di‐p‐benzoatoporphyrin MOL is reported to afford SNAP/MOL for enhanced cancer radiotherapy. Under X‐ray irradiation, SNAP/MOL efficiently generates superoxide anion (O2−.) and releases nitric oxide (NO) in a spatio‐temporally synchronized fashion. The released NO rapidly reacts with O2−. to form long‐lived and highly cytotoxic peroxynitrite which diffuses freely to the cell nucleus and efficiently causes DNA double‐strand breaks. Meanwhile, the sustained release of NO from SNAP/MOL in the tumor microenvironment relieves tumor hypoxia to reduce radioresistance of tumor cells. Consequently, SNAP/MOL plus low‐dose X‐ray irradiation efficiently inhibits tumor growth and reduces metastasis in colorectal and triple‐negative breast cancer models.
ISSN:2198-3844

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