1. Synergistic cerium oxide nanozymes: targeting DNA damage and alleviating tumor hypoxia for improved NSCLC radiotherapy efficiency.
- Author
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Liu, Jie, Liu, Chengxiang, Tang, Jinghua, Chen, Qiao, Yu, Yan, Dong, Yan, Hao, Jie, and Wu, Wei
- Subjects
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QUERCETIN , *CERIUM oxides , *DNA damage , *SYNTHETIC enzymes , *NON-small-cell lung carcinoma , *HYPOXEMIA , *REVERSE transcriptase - Abstract
Radiotherapy (RT) is one of the important treatment modalities for non-small cell lung cancer (NSCLC). However, the maximum radiation dose that NSCLC patient can receive varies little. Therefore, the exploitation of novel RT sensitization approaches is a critical need for the clinical treatment. RT resistance in NSCLC is linked to tumor microenvironment (TME) hypoxia, cell cycle arrest and associated genetic alterations. Here, we designed a novel method for targeted delivery of quercetin (QT) and CeO2 to enhance RT sensitivity. We loaded QT into CeO2@ZIF-8-HA nanoparticles to prevent its degradation in the circulatory system and successfully delivered QT and CeO2 targeted to NSCLC tumors. Under the protection and targeted delivery of Zeolitic Imidazolate Framework-8 (ZIF-8), the nanocomplexes exhibited excellent catalytic mimetic activity in decomposing H2O2 into O2, thus significantly reversing the hypoxia of TME, while the radiosensitizer QT caused DNA damage directly after RT. In a subcutaneous tumor model, CeO2@ZIF-8-HA overcame radiation resistance and enhanced therapeutic efficacy. This multiple sensitization strategy combining delivery of QT and CeO2@ZIF-8-HA nanozymes opens a promising approach for RT of NSCLC. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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