TME-Activated MnO2/Pt Nanoplatform of Hydroxyl Radical and Oxygen Generation to Synergistically Promote Radiotherapy and MR Imaging of Glioblastoma

Abstract

Lijuan Chen,1,* Mingbo Liu,2,* Yunjuan Wang,3,4,* Wei Wei,1 Yaqiong Li,5 Yan Bai,1 Xuan Yu,1 Lei Jiao,6 Meiyun Wang1,4 1Department of Medical Imaging, Henan Provincial People’s Hospital & the People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, People’s Republic of China; 2Department of Radiotherapy, Henan Provincial People’s Hospital & the People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, People’s Republic of China; 3School of Life Sciences, Henan University, North Section of Jinming Avenue, Kaifeng, Henan, 475004, People’s Republic of China; 4Institute of Biomedicine, Henan Academy of Sciences, Zhengzhou, Henan, 450046, People’s Republic of China; 5Department of Pharmacy, Henan Provincial People’s Hospital & the People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, People’s Republic of China; 6Institute of Molecular Metrology, College of Chemistry and Chemical Engineering, Qingdao University, Qingdao, Shandong, 266071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Meiyun Wang, The Department of Medical Imaging, Henan Provincial People’s Hospital & the People’s Hospital of Zhengzhou University, No. 7, WeiWu Road, Zhengzhou, Henan, 450003, People’s Republic of China, Email [email protected]: Radiotherapy (RT) is currently recognized as an important treatment for glioblastoma (GBM), however, it is associated with several challenges. One of these challenges is the radioresistance caused by hypoxia, whereas the other is the low conversion efficiency of the strongly oxidized hydroxyl radical (•OH), which is produced by the decomposition of water due to high-energy X-ray radiation. These factors significantly limit the clinical effectiveness of radiotherapy.Results: To address these limitations, we developed a highly stable and efficient nanoplatform (MnO2/Pt@BSA). Compared to MnO2@BSA, this platform demonstrates high stability, a high yield of oxygen (O2), enhanced production of •OH, and reduced clearance of •OH. The system exhibited increased O2 production in vitro and significantly improved oxygen production efficiency within 100 s at the Pt loading of 38.7%. Furthermore, compared with MnO2, the expression rate of hypoxia-inducible factor (HIF-1α) in glioma cells treated with MnO2/Pt decreased by half. Additionally, the system promotes •OH generation and consumes glutathione (GSH), thereby inhibiting the clearance of •OH and enhancing its therapeutic effect. Moreover, the degradation of the nanoplatform produces Mn2+, which serves as a magnetic resonance imaging (MRI) contrast agent with a T1-weighted enhancement effect at the tumor site. The nanoplatform exhibited excellent biocompatibility and performed multiple functions related to radiotherapy, with simpler components. In U87 tumor bearing mice model, we utilized MnO2/Pt nanocatalysis to enhance the therapeutic effect of radiotherapy on GBM.Conclusion: This approach represents a novel and effective strategy for enhancing radiotherapy in gliomas, thereby advancing the field of catalytic radiotherapy and glioma treatment.Keywords: radiotherapy, glioblastoma, MnO2/Pt@BSA nanoplatform, nanocatalysis

Keywords

• radiotherapy
• glioblastoma
• mno2/pt@bsa nanoplatform
• nanocatalysis