Synergistic cerium oxide nanozymes: targeting DNA damage and alleviating tumor hypoxia for improved NSCLC radiotherapy efficiency
Jie Liu, Chengxiang Liu, Jinghua Tang, Qiao Chen, Yan Yu, Yan Dong, Jie Hao, Wei Wu
Abstract
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 CeO 2 to enhance RT sensitivity. We loaded QT into CeO 2 @ZIF-8-HA nanoparticles to prevent its degradation in the circulatory system and successfully delivered QT and CeO 2 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 H 2 O 2 into O 2 , thus significantly reversing the hypoxia of TME, while the radiosensitizer QT caused DNA damage directly after RT. In a subcutaneous tumor model, CeO 2 @ZIF-8-HA overcame radiation resistance and enhanced therapeutic efficacy. This multiple sensitization strategy combining delivery of QT and CeO 2 @ZIF-8-HA nanozymes opens a promising approach for RT of NSCLC.