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A platform for research: civil engineering, architecture and urbanism
Nitric Oxide‐Releasing Nanoscale Metal‐Organic Layer Overcomes Hypoxia and Reactive Oxygen Species Diffusion Barriers to Enhance Cancer Radiotherapy
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.
Nitric Oxide‐Releasing Nanoscale Metal‐Organic Layer Overcomes Hypoxia and Reactive Oxygen Species Diffusion Barriers to Enhance Cancer Radiotherapy
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.
Nitric Oxide‐Releasing Nanoscale Metal‐Organic Layer Overcomes Hypoxia and Reactive Oxygen Species Diffusion Barriers to Enhance Cancer Radiotherapy
Xiong, Yuxuan (author) / Li, Jinhong (author) / Jiang, Xiaomin (author) / Zhen, Wenyao (author) / Ma, Xin (author) / Lin, Wenbin (author)
Advanced Science ; 12
2025-02-01
14 pages
Article (Journal)
Electronic Resource
English
British Library Online Contents | 2017
British Library Online Contents | 2017
| British Library Online Contents | 1999